Advertisement

Journal of Molecular Neuroscience

, Volume 67, Issue 2, pp 312–342 | Cite as

Sex-Specific Differences in Redox Homeostasis in Brain Norm and Disease

  • Joanna A. RuszkiewiczEmail author
  • Antonio Miranda-Vizuete
  • Alexey A. Tinkov
  • Margarita G. Skalnaya
  • Anatoly V. Skalny
  • Aristides Tsatsakis
  • Michael Aschner
Article
  • 146 Downloads

Abstract

Sex differences in brain physiology and by inference various pathologies are generally recognized, however frequently ignored in epidemiological and experimental studies, leading to numerous data gaps. As a consequence, the mechanisms underlying sexual dimorphism of neurological diseases remain largely unknown. Several cellular and molecular pathways linked to the etiology and pathogenesis of various brain disorders have been recently described as sex-specific. Here, we review the evidence for sex differences in brain redox homeostasis, which is an important factor in brain physiology and disease. First, we focus on sex-specific differences in the healthy brain regarding popular redox balance markers, including reactive oxygen and nitrogen species, oxidative damage, and antioxidant status. We also review the modulatory effect of steroid sex hormones on these markers. Lastly, we approach the sex-specific changes in brain redox homeostasis in disease and discuss the possibility that differential redox response contributes to the sexual dimorphism of neurological disorders.

Keywords

Oxidative stress Antioxidant Sex Brain Neurodegeneration Neurotoxicity 

Abbreviations

AA

Ascorbic acid

β-Amyloid peptide

AD

Alzheimer disease

ADHD

Attention deficit hyperactivity disorder

ALS

Amyotrophic lateral sclerosis

AP-1

Activator protein-1

APP

Amyloid precursor protein

ARE

Antioxidant response element

As

Arsenic

ASD

Autism spectrum disorder

ATP

Adenosine triphosphate

BOAA

β-N-Oxalyl-amino-L-alanine

BPA

Bisphenol A

CAT

Catalase

CB

Cerebrum

CCI

Controlled cortical impact

CN

Caudate nucleus

CNS

Central nervous system

COX

Cytochrome c oxidase

CP

Caudate putamen

CPF

Chlorpyrifos

CREB

Cyclic AMP response element binding protein

CSF

Cerebrospinal fluid

CV

Cerebellum

CX

Cortex

DBL

Lewy body dementia

DE

Diesel exhaust

DHT

Dihydrotestosterone

E2

17β-estradiol

ED

Embryonic day

EDC

Endocrine disrupting chemical

ER

Estrogen receptor

ETC

Electron transport chain

EtOH

Ethanol

EW

Ethanol withdrawal

F2-IsoP

F2-isoprostane

FALS

Familial ALS

FC

Frontal cortex

Fe

Iron

FMO

Flavin-containing monooxygenase

FRAP

Ferric reducing antioxidant power

GCL

Glutamate-cysteine ligase

GDX

Gonadectomy

γGT

γ-Glutamyl transferase

GSH

Glutathione reduced

GSSH

Glutathione oxidized

GPX

Glutathione peroxidase

GR

Glutathione reductase

GRX

Glutaredoxin

GS

Glutathione synthase

GST

Glutathione S-transferase

Hcy

Homocysteine

HD

Huntington’s disease

HI

Hypoxia-ischemia

HIE

Hypoxic-ischemic encephalopathy

4-HNE

4-hydroxynonenal

HO-1

Heme oxygenase 1

HP

Hippocampus

HT

Hypothalamus

ICH

Intracerebral hemorrhage

iNOS

Inducible nitric oxide synthase

IQ

Intelligence quotient

KEAP 1

Kelch-like ECH-associated protein 1

KI

Knock-in

LPO

Lipid peroxidation

MB

Midbrain

MCAO

Middle cerebral artery occlusion

MDD

Major depressive disorder

MeHg

Methylmercury

Mn

Manganese

MO

Medulla oblongata

MPP+

1-methyl-4-phenylpyridinium

MPTP

1-methyl-4-phenyl-1, 2, 3, 6, tetrahydro-pyridine

NA

Nucleus accumbens

NADH/NAD

Nicotinamide adenine dinucleotide

NF-κB

Nuclear factor-κB

NIH

National Institutes of Health

nNOS

Neuronal nitric oxide synthase

NO

Nitric oxide

NOS

Nitric oxide synthase

NOx

Stable nitric oxide metabolites, nitrite (NO2-) + nitrate (NO3-)

NRF2

Nuclear factor erythroid 2-related factor 2

3-NT

3-nitrotyrosine

NQO1

NAD(P)H dehydrogenase (quinone) 1

OB

Olfactory bulb

6-OHDA

6-hydroxydopamine

ONS

Oxidative -nitrosative stress

OP

Organophosphate pesticide

OVX

Ovariectomy

PCB

Polychlorinated biphenyl

PD

Parkinson disease

PFAS

Poly- and perfluoroalkyl substances

PFC

Prefrontal cortex

PFOA

Perfluorooctanoic acid

PFOS

Perfluorooctane sulfonate

PND

Postnatal day

Poly(I:C)

Polyinosinic/polycytidylic acid

PON

Paraoxonase

PROG

Progesterone

PRX

Peroxiredoxin

PUS

Peripubertal unpredictable stress

rNPCs

Rat neural progenitor cells

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

SCZ

schizophrenia

SE

status epilepticus

SN

substantia nigra

SOD

Superoxide dismutase

SOD1

Cu/Zn-superoxide dismutase

SOD2

Mn-superoxide dismutase

ST

Striatum

TAC

Total antioxidant capacity

TBARS

Thiobarbituric acid reactive substances

TBBPA

Tetrabromobisphenol A

TBI

Traumatic brain injury

TCDD

2,3,7,8-tetrachlorodibenzo-p-dioxin

TEST

Testosterone

Tg

Transgenic

TRX

Thioredoxin

TRXR

Thioredoxin reductase

TP

Testosterone propionate

UA

Uric acid

VDR

Vitamin D receptor

wt

Wild-type

Notes

Funding information

MA was supported by grants from the National Institute of Environmental Health Sciences, NIEHS R01ES07331, NIEHS R01ES10563, and NIEHS R01ES020852.

References

  1. Abel KM, Drake R, Goldstein JM (2010) Sex differences in schizophrenia. Int Rev Psychiatry 22:417–428.  https://doi.org/10.3109/09540261.2010.515205 Google Scholar
  2. Abramov JP, Tran A, Shapiro AM, Wells PG (2012) Protective role of endogenous catalase in baseline and phenytoin-enhanced neurodevelopmental and behavioral deficits initiated in utero and in aged mice. Reprod Toxicol 33:361–373.  https://doi.org/10.1016/j.reprotox.2012.01.010 Google Scholar
  3. Adzic M, Mitic M, Radojcic M (2017) Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus. Brain Res 1671:77–84.  https://doi.org/10.1016/j.brainres.2017.07.007 Google Scholar
  4. Aggarwal R, Medhi B, Pathak A, Dhawan V, Chakrabarti A (2008) Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice. J Pharm Pharmacol 60:731–737.  https://doi.org/10.1211/jpp.60.6.0008 Google Scholar
  5. Ahlbom E, Grandison L, Bonfoco E, Zhivotovsky B, Ceccatelli S (1999) Androgen treatment of neonatal rats decreases susceptibility of cerebellar granule neurons to oxidative stress in vitro. Eur J Neurosci 11:1285–1291Google Scholar
  6. Ahlbom E, Prins GS, Ceccatelli S (2001) Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res 892:255–262Google Scholar
  7. Airas L (2015) Hormonal and gender-related immune changes in multiple sclerosis. Acta Neurol Scand 132:62–70.  https://doi.org/10.1111/ane.12433 Google Scholar
  8. Akhter H, Ballinger C, Liu N, van Groen T, Postlethwait EM, Liu RM (2015) Cyclic ozone exposure induces gender-dependent neuropathology and memory decline in an animal model of Alzheimer’s disease. Toxicol Sci 147:222–234.  https://doi.org/10.1093/toxsci/kfv124 Google Scholar
  9. Akyol O et al (2002) The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuro-Psychopharmacol Biol Psychiatry 26:995–1005Google Scholar
  10. Al Sweidi S, Sanchez MG, Bourque M, Morissette M, Dluzen D, Di Paolo T (2012) Oestrogen receptors and signalling pathways: implications for neuroprotective effects of sex steroids in Parkinson's disease. J Neuroendocrinol 24:48–61.  https://doi.org/10.1111/j.1365-2826.2011.02193.x Google Scholar
  11. Alabarse PV et al (2011) Oxidative stress in the brain of reproductive male rats during aging. Exp Gerontol 46:241–248.  https://doi.org/10.1016/j.exger.2010.10.009 Google Scholar
  12. Alfonso-Loeches S, Pascual M, Guerri C (2013) Gender differences in alcohol-induced neurotoxicity and brain damage. Toxicology 311:27–34.  https://doi.org/10.1016/j.tox.2013.03.001 Google Scholar
  13. Al-Gubory KH, Garrel C (2016) Sex-specific divergence of antioxidant pathways in fetal brain, liver, and skeletal muscles. Free Radic Res 50:366–373.  https://doi.org/10.3109/10715762.2015.1130224 Google Scholar
  14. Ali SS, Xiong C, Lucero J, Behrens MM, Dugan LL, Quick KL (2006) Gender differences in free radical homeostasis during aging: shorter-lived female C57BL6 mice have increased oxidative stress. Aging Cell 5:565–574.  https://doi.org/10.1111/j.1474-9726.2006.00252.x Google Scholar
  15. Allan AM, Hafez AK, Labrecque MT, Solomon ER, Shaikh MN, Zheng X, Ali A (2015) Sex-dependent effects of developmental arsenic exposure on methylation capacity and methylation regulation of the glucocorticoid receptor system in the embryonic mouse brain. Toxicol Rep 2:1376–1390.  https://doi.org/10.1016/j.toxrep.2015.10.003 Google Scholar
  16. Allison JH, Stewart MA (1973) Myo-inositol and ascorbic acid in developing rat brain. J Neurochem 20:1785–1788Google Scholar
  17. Amram N et al (2016) Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory. Mol Psychiatry 21:1467–1476.  https://doi.org/10.1038/mp.2015.208 Google Scholar
  18. Angelova PR, Abramov AY (2016) Functional role of mitochondrial reactive oxygen species in physiology. Free Radic Biol Med 100:81–85.  https://doi.org/10.1016/j.freeradbiomed.2016.06.005 Google Scholar
  19. Azcoitia I, DonCarlos LL, Garcia-Segura LM (2003) Are gonadal steroid hormones involved in disorders of brain aging? Aging Cell 2:31–37Google Scholar
  20. Bagchi D, Balmoori J, Bagchi M, Ye X, Williams CB, Stohs SJ (2002) Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice. Toxicology 175:73–82Google Scholar
  21. Bardullas U, Limon-Pacheco JH, Giordano M, Carrizales L, Mendoza-Trejo MS, Rodriguez VM (2009) Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice. Toxicol Appl Pharmacol 239:169–177.  https://doi.org/10.1016/j.taap.2008.12.004 Google Scholar
  22. Bauzá-Thorbrügge M, M Galmés-Pascual B, Sbert-Roig M, J García-Palmer F, Gianotti M, M Proenza A, Lladó I (2017) Antioxidant peroxiredoxin 3 expression is regulated by 17beta-estradiol in rat white adipose tissue. J Steroid Biochem Mol Biol 172:9–19.  https://doi.org/10.1016/j.jsbmb.2017.05.008 Google Scholar
  23. Bayir H, Marion DW, Puccio AM, Wisniewski SR, Janesko KL, Clark RS, Kochanek PM (2004) Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. J Neurotrauma 21:1–8.  https://doi.org/10.1089/089771504772695896 Google Scholar
  24. Bekhbat M, Neigh GN (2018) Sex differences in the neuro-immune consequences of stress: focus on depression and anxiety. Brain Behav Immun 67:1–12.  https://doi.org/10.1016/j.bbi.2017.02.006 Google Scholar
  25. Benner MJ, Drew RE, Hardy RW, Robison BD (2010) Zebrafish (Danio rerio) vary by strain and sex in their behavioral and transcriptional responses to selenium supplementation. Comp Biochem Physiol A Mol Integr Physiol 157:310–318.  https://doi.org/10.1016/j.cbpa.2010.07.016 Google Scholar
  26. Bertholet L, Meunier C, Preissmann D, Schenk F (2014) Sex biased spatial strategies relying on the integration of multimodal cues in a rat model of schizophrenia: impairment in predicting future context? Behav Brain Res 262:109–117.  https://doi.org/10.1016/j.bbr.2013.12.039 Google Scholar
  27. Biasibetti R et al (2017) Hippocampal changes in STZ-model of Alzheimer’s disease are dependent on sex. Behav Brain Res 316:205–214.  https://doi.org/10.1016/j.bbr.2016.08.057 Google Scholar
  28. Bjornstrom L, Sjoberg M (2005) Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol 19:833–842.  https://doi.org/10.1210/me.2004-0486 Google Scholar
  29. Bolton JL, Auten RL, Bilbo SD (2014) Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring. Brain Behav Immun 37:30–44.  https://doi.org/10.1016/j.bbi.2013.10.029 Google Scholar
  30. Bolton JL et al (2017) Gestational exposure to air pollution alters cortical volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner. Front Synaptic Neurosci 9:10.  https://doi.org/10.3389/fnsyn.2017.00010 Google Scholar
  31. Borovkova EI, Antipova NV, Komeenko TV, Shakhparonov MI, Borovkov IM (2017) Paraoxonase: the universal factor of antioxidant defense in human body. Vestn Ross Akad Med Nauk 72:5–10.  https://doi.org/10.15690/vramn764 Google Scholar
  32. Borras C, Sastre J, Garcia-Sala D, Lloret A, Pallardo FV, Vina J (2003) Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med 34:546–552Google Scholar
  33. Brocardo PS, Boehme F, Patten A, Cox A, Gil-Mohapel J, Christie BR (2012) Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise. Neuropharmacology 62:1607–1618.  https://doi.org/10.1016/j.neuropharm.2011.10.006 Google Scholar
  34. Brooks CE, Clayton JA (2017) Sex/gender influences on the nervous system: basic steps toward clinical progress. J Neurosci Res 95:14–16.  https://doi.org/10.1002/jnr.23902 Google Scholar
  35. Buettner GR (2011) Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide. Anti Cancer Agents Med Chem 11:341–346Google Scholar
  36. Cacabelos D et al (2016) Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS. Acta Neuropathol Commun 4:3.  https://doi.org/10.1186/s40478-015-0271-6 Google Scholar
  37. Cahill L (2006) Why sex matters for neuroscience. Nat Rev Neurosci 7:477–484.  https://doi.org/10.1038/nrn1909 Google Scholar
  38. Cahill L (2017) An issue whose time has come. J Neurosci Res 95:12–13.  https://doi.org/10.1002/jnr.23972 Google Scholar
  39. Candeias E et al (2016) Middle-aged diabetic females and males present distinct susceptibility to Alzheimer disease-like pathology. Mol Neurobiol.  https://doi.org/10.1007/s12035-016-0155-1
  40. Cannon JR, Greenamyre JT (2011) The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol Sci 124:225–250.  https://doi.org/10.1093/toxsci/kfr239 Google Scholar
  41. Capel ID, Smallwood AE (1983) Sex differences in the glutathione peroxidase activity of various tissues of the rat. Res Commun Chem Pathol Pharmacol 40:367–378Google Scholar
  42. Carlstrom L, Ke ZJ, Unnerstall JR, Cohen RS, Pandey SC (2001) Estrogen modulation of the cyclic AMP response element-binding protein pathway. Effects of long-term and acute treatments. Neuroendocrinology 74:227–243.  https://doi.org/10.1159/000054690 Google Scholar
  43. Carrillo MC, Kanai S, Sato Y, Kitani K (1992) Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat. Mech Ageing Dev 65:187–198Google Scholar
  44. Casado A, Encarnacion Lopez-Fernandez M, Concepcion Casado M, de La Torre R (2008) Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res 33:450–458.  https://doi.org/10.1007/s11064-007-9453-3 Google Scholar
  45. Castagne V, Cuenod M, Do KQ (2004) An animal model with relevance to schizophrenia: sex-dependent cognitive deficits in osteogenic disorder-Shionogi rats induced by glutathione synthesis and dopamine uptake inhibition during development. Neuroscience 123:821–834Google Scholar
  46. Chakraborti A, Gulati K, Banerjee BD, Ray A (2007) Possible involvement of free radicals in the differential neurobehavioral responses to stress in male and female rats. Behav Brain Res 179:321–325.  https://doi.org/10.1016/j.bbr.2007.02.018 Google Scholar
  47. Chakraborti A, Gulati K, Ray A (2014) Possible role of nitric oxide (NO) in the regulation of gender related differences in stress induced anxiogenesis in rats. Nitric Oxide Biol Chem 43:74–80.  https://doi.org/10.1016/j.niox.2014.08.005 Google Scholar
  48. Chambliss KL, Shaul PW (2002) Estrogen modulation of endothelial nitric oxide synthase. Endocr Rev 23:665–686.  https://doi.org/10.1210/er.2001-0045 Google Scholar
  49. Charradi K, Mahmoudi M, Bedhiafi T, Kadri S, Elkahoui S, Limam F, Aouani E (2017) Dietary supplementation of grape seed and skin flour mitigates brain oxidative damage induced by a high-fat diet in rat: gender dependency. Biomed Pharmacother 87:519–526.  https://doi.org/10.1016/j.biopha.2017.01.015 Google Scholar
  50. Charriaut-Marlangue C, Besson VC, Baud O (2017) Sexually dimorphic outcomes after neonatal stroke and hypoxia-ischemia. Int J Mol Sci 19.  https://doi.org/10.3390/ijms19010061
  51. Chauhan A, Moser H, McCullough LD (2017) Sex differences in ischaemic stroke: potential cellular mechanisms. Clin Sci (Lond) 131:533–552.  https://doi.org/10.1042/cs20160841 Google Scholar
  52. Chen TY, Tsai KL, Lee TY, Chiueh CC, Lee WS, Hsu C (2010) Sex-specific role of thioredoxin in neuroprotection against iron-induced brain injury conferred by estradiol. Stroke 41:160–165.  https://doi.org/10.1161/strokeaha.109.562850 Google Scholar
  53. Chen Y, Ji LL, Liu TY, Wang ZT (2011) Evaluation of gender-related differences in various oxidative stress enzymes in mice. Chin J Phys 54:385–390.  https://doi.org/10.4077/cjp.2011.amm080 Google Scholar
  54. Chen CS, Tseng YT, Hsu YY, Lo YC (2013) Nrf2-Keap1 antioxidant defense and cell survival signaling are upregulated by 17beta-estradiol in homocysteine-treated dopaminergic SH-SY5Y cells. Neuroendocrinology 97:232–241.  https://doi.org/10.1159/000342692 Google Scholar
  55. Chisu V, Manca P, Zedda M, Lepore G, Gadau S, Farina V (2006) Effects of testosterone on differentiation and oxidative stress resistance in C1300 neuroblastoma cells. Neuro Endocrinol Lett 27:807–812Google Scholar
  56. Chiu CC, Chen CH, Huang MC, Chen PY, Tsai CJ, Lu ML (2012) The relationship between serum uric acid concentration and metabolic syndrome in patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 32:585–592.  https://doi.org/10.1097/JCP.0b013e3182664e64 Google Scholar
  57. Chiu YH et al (2016) Prenatal particulate air pollution and neurodevelopment in urban children: examining sensitive windows and sex-specific associations. Environ Int 87:56–65.  https://doi.org/10.1016/j.envint.2015.11.010 Google Scholar
  58. Christensen J, Kjeldsen MJ, Andersen H, Friis ML, Sidenius P (2005) Gender differences in epilepsy. Epilepsia 46:956–960.  https://doi.org/10.1111/j.1528-1167.2005.51204.x Google Scholar
  59. Chung WC, Auger AP (2013) Gender differences in neurodevelopment and epigenetics. Pflugers Arch 465:573–584.  https://doi.org/10.1007/s00424-013-1258-4 Google Scholar
  60. Clayton JA, Collins FS (2014) Policy: NIH to balance sex in cell and animal studies. Nature 509:282–283Google Scholar
  61. Cole TB et al (2016) Sex and genetic differences in the effects of acute diesel exhaust exposure on inflammation and oxidative stress in mouse brain. Toxicology 374:1–9.  https://doi.org/10.1016/j.tox.2016.11.010 Google Scholar
  62. Costa LG, de Laat R, Dao K, Pellacani C, Cole TB, Furlong CE (2014) Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection, Neurotoxicology. 43:3–9.  https://doi.org/10.1016/j.neuro.2013.08.011
  63. Dadheech G, Mishra S, Gautam S, Sharma P (2006) Oxidative stress, alpha-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian J Clin Biochem 21:34–38.  https://doi.org/10.1007/bf02912908 Google Scholar
  64. Dadheech G, Mishra S, Gautam S, Sharma P (2008) Evaluation of antioxidant deficit in schizophrenia. Indian J Psychiatry 50:16–20.  https://doi.org/10.4103/0019-5545.39753 Google Scholar
  65. Dan Dunn J, Alvarez LA, Zhang X, Soldati T (2015) Reactive oxygen species and mitochondria: a nexus of cellular homeostasis. Redox Biol 6:472–485.  https://doi.org/10.1016/j.redox.2015.09.005 Google Scholar
  66. Das M, Dixit R, Seth PK, Mukhtar H (1981) Glutathione-S-transferase activity in the brain: species, sex, regional, and age differences. J Neurochem 36:1439–1442Google Scholar
  67. Davies W (2014) Sex differences in attention deficit hyperactivity disorder: candidate genetic and endocrine mechanisms. Front Neuroendocrinol 35:331–346.  https://doi.org/10.1016/j.yfrne.2014.03.003 Google Scholar
  68. Davies W, Wilkinson LS (2006) It is not all hormones: alternative explanations for sexual differentiation of the brain. Brain Res 1126:36–45.  https://doi.org/10.1016/j.brainres.2006.09.105 Google Scholar
  69. De Felice A, Greco A, Calamandrei G, Minghetti L (2016) Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism. J Neuroinflammation 13:149.  https://doi.org/10.1186/s12974-016-0617-4 Google Scholar
  70. de la Torre MR, Casado A, Lopez-Fernandez ME, Carrascosa D, Casado MC, Venarucci D, Venarucci V (1996) Human aging brain disorders: role of antioxidant enzymes. Neurochem Res 21:885–888Google Scholar
  71. Dean SL, McCarthy MM (2008) Steroids, sex and the cerebellar cortex: implications for human disease. Cerebellum 7:38–47.  https://doi.org/10.1007/s12311-008-0003-6 Google Scholar
  72. Demarest TG, McCarthy MM (2015) Sex differences in mitochondrial (dys)function: implications for neuroprotection. J Bioenerg Biomembr 47:173–188.  https://doi.org/10.1007/s10863-014-9583-7 Google Scholar
  73. Demarest TG, Schuh RA, Waddell J, McKenna MC, Fiskum G (2016a) Sex-dependent mitochondrial respiratory impairment and oxidative stress in a rat model of neonatal hypoxic-ischemic encephalopathy. J Neurochem 137:714–729.  https://doi.org/10.1111/jnc.13590 Google Scholar
  74. Demarest TG, Schuh RA, Waite EL, Waddell J, McKenna MC, Fiskum G (2016b) Sex dependent alterations in mitochondrial electron transport chain proteins following neonatal rat cerebral hypoxic-ischemia. J Bioenerg Biomembr 48:591–598.  https://doi.org/10.1007/s10863-016-9678-4 Google Scholar
  75. Demarest TG, Waite EL, Kristian T, Puche AC, Waddell J, McKenna MC, Fiskum G (2016c) Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia-ischemia. Neuroscience 335:103–113.  https://doi.org/10.1016/j.neuroscience.2016.08.026 Google Scholar
  76. Deponte M (2013) Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 1830:3217–3266.  https://doi.org/10.1016/j.bbagen.2012.09.018 Google Scholar
  77. Deshmukh A, Rosenbloom MJ, Sassoon S, O'Reilly A, Pfefferbaum A, Sullivan EV (2003) Alcoholic men endorse more DSM-IV withdrawal symptoms than alcoholic women matched in drinking history. J Stud Alcohol 64:375–379Google Scholar
  78. Di Domenico F et al (2012) Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion. J Neurochem 121:680–692.  https://doi.org/10.1111/j.1471-4159.2012.07721.x Google Scholar
  79. Di Somma C et al (2017) Vitamin D and neurological diseases: an endocrine view. Int J Mol Sci 18.  https://doi.org/10.3390/ijms18112482
  80. Diwakar L, Kenchappa RS, Annepu J, Ravindranath V (2007) Downregulation of glutaredoxin but not glutathione loss leads to mitochondrial dysfunction in female mice CNS: implications in excitotoxicity. Neurochem Int 51:37–46.  https://doi.org/10.1016/j.neuint.2007.03.008 Google Scholar
  81. Dkhil MA, Al-Shaebi EM, Lubbad MY, Al-Quraishy S (2016) Impact of sex differences in brain response to infection with Plasmodium berghei. Parasitol Res 115:415–422.  https://doi.org/10.1007/s00436-015-4803-6 Google Scholar
  82. Donner NC, Lowry CA (2013) Sex differences in anxiety and emotional behavior. Pflugers Arch 465:601–626.  https://doi.org/10.1007/s00424-013-1271-7 Google Scholar
  83. Dorner JL, Miller BR, Barton SJ, Brock TJ, Rebec GV (2007) Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington’s disease. Behav Brain Res 178:90–97.  https://doi.org/10.1016/j.bbr.2006.12.004 Google Scholar
  84. Du L et al (2004) Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway. J Biol Chem 279:38563–38570.  https://doi.org/10.1074/jbc.M405461200 Google Scholar
  85. Dukhande VV, Isaac AO, Chatterji T, Lai JC (2009) Reduced glutathione regenerating enzymes undergo developmental decline and sexual dimorphism in the rat cerebral cortex. Brain Res 1286:19–24.  https://doi.org/10.1016/j.brainres.2009.05.029 Google Scholar
  86. Ebrahimian T, He Y, Schiffrin EL, Touyz RM (2007) Differential regulation of thioredoxin and NAD(P)H oxidase by angiotensin II in male and female mice. J Hypertens 25:1263–1271.  https://doi.org/10.1097/HJH.0b013e3280acac60 Google Scholar
  87. Edwin EE, Diplock AT, Bunyan J, Green J (1961) Studies on vitamin E. 6. The distribution of vitamin E in the rat and the effect of alpha-tocopherol and dietary selenium on ubiquinone and ubichromenol in tissues. Biochem J 79:91–105Google Scholar
  88. Ehrenbrink G, Hakenhaar FS, Salomon TB, Petrucci AP, Sandri MR, Benfato MS (2006) Antioxidant enzymes activities and protein damage in rat brain of both sexes. Exp Gerontol 41:368–371.  https://doi.org/10.1016/j.exger.2006.02.007 Google Scholar
  89. El-Missiry MA, Othman AI, Al-Abdan MA, El-Sayed AA (2014) Melatonin ameliorates oxidative stress, modulates death receptor pathway proteins, and protects the rat cerebrum against bisphenol-A-induced apoptosis. J Neurol Sci 347:251–256.  https://doi.org/10.1016/j.jns.2014.10.009 Google Scholar
  90. Emiliani FE, Sedlak TW, Sawa A (2014) Oxidative stress and schizophrenia: recent breakthroughs from an old story. Curr Opin Psychiatry 27:185–190.  https://doi.org/10.1097/yco.0000000000000054 Google Scholar
  91. Engel SM, Miodovnik A, Canfield RL, Zhu C, Silva MJ, Calafat AM, Wolff MS (2010) Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ Health Perspect 118:565–571.  https://doi.org/10.1289/ehp.0901470 Google Scholar
  92. Engler-Chiurazzi EB, Brown CM, Povroznik JM, Simpkins JW (2017) Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury. Prog Neurobiol 157:188–211.  https://doi.org/10.1016/j.pneurobio.2015.12.008 Google Scholar
  93. Erikson KM, Dorman DC, Lash LH, Dobson AW, Aschner M (2004) Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner. Biol Trace Elem Res 100:49–62.  https://doi.org/10.1385/bter:100:1:049 Google Scholar
  94. Evans SF et al (2014) Prenatal bisphenol A exposure and maternally reported behavior in boys and girls. Neurotoxicology 45:91–99.  https://doi.org/10.1016/j.neuro.2014.10.003 Google Scholar
  95. Evsen MS et al (2013) Effects of estrogen, estrogen/progesteron combination and genistein treatments on oxidant/antioxidant status in the brain of ovariectomized rats. Eur Rev Med Pharmacol Sci 17:1869–1873Google Scholar
  96. Ferri SL, Abel T, Brodkin ES (2018) Sex differences in autism spectrum disorder: a review. Curr Psychiatry Rep 20:9.  https://doi.org/10.1007/s11920-018-0874-2 Google Scholar
  97. Ferris DC, Kume-Kick J, Russo-Menna I, Rice ME (1995) Gender differences in cerebral ascorbate levels and ascorbate loss in ischemia. Neuroreport 6:1485–1489Google Scholar
  98. Flaherty ML et al (2006) Long-term mortality after intracerebral hemorrhage. Neurology 66:1182–1186.  https://doi.org/10.1212/01.wnl.0000208400.08722.7c Google Scholar
  99. Fonnum F, Mariussen E (2009) Mechanisms involved in the neurotoxic effects of environmental toxicants such as polychlorinated biphenyls and brominated flame retardants. J Neurochem 111:1327–1347.  https://doi.org/10.1111/j.1471-4159.2009.06427.x Google Scholar
  100. Foroud T, Gray J, Ivashina J, Conneally PM (1999) Differences in duration of Huntington's disease based on age at onset. J Neurol Neurosurg Psychiatry 66:52–56Google Scholar
  101. Frutiger K, Lukas TJ, Gorrie G, Ajroud-Driss S, Siddique T (2008) Gender difference in levels of Cu/Zn superoxide dismutase (SOD1) in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9:184–187.  https://doi.org/10.1080/17482960801984358 Google Scholar
  102. Gagliardi S et al (2011) Flavin-containing monooxygenase mRNA levels are up-regulated in als brain areas in SOD1-mutant mice. Neurotox Res 20:150–158.  https://doi.org/10.1007/s12640-010-9230-y Google Scholar
  103. Gaignard P et al (2015) Effect of sex differences on brain mitochondrial function and its suppression by ovariectomy and in aged mice. Endocrinology 156:2893–2904.  https://doi.org/10.1210/en.2014-1913 Google Scholar
  104. Gaignard P, Liere P, Therond P, Schumacher M, Slama A, Guennoun R (2017) Role of sex hormones on brain mitochondrial function, with special reference to aging and neurodegenerative diseases. Front Aging Neurosci 9:406.  https://doi.org/10.3389/fnagi.2017.00406 Google Scholar
  105. Gao X, O'Reilly EJ, Schwarzschild MA, Ascherio A (2016) Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology 86:520–526.  https://doi.org/10.1212/wnl.0000000000002351 Google Scholar
  106. Gassman NR (2017) Induction of oxidative stress by bisphenol A and its pleiotropic effects. Environ Mol Mutagen 58:60–71.  https://doi.org/10.1002/em.22072 Google Scholar
  107. Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT (2011) Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 14:123–130.  https://doi.org/10.1017/s1461145710000805 Google Scholar
  108. Gillette R, Reilly MP, Topper VY, Thompson LM, Crews D, Gore AC (2017) Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero. Horm Behav 87:8–15.  https://doi.org/10.1016/j.yhbeh.2016.10.011 Google Scholar
  109. Gillies GE, McArthur S (2010) Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacol Rev 62:155–198.  https://doi.org/10.1124/pr.109.002071 Google Scholar
  110. Gimenez-Llort L, Garcia Y, Buccieri K, Revilla S, Sunol C, Cristofol R, Sanfeliu C (2010) Gender-specific Neuroimmunoendocrine response to treadmill exercise in 3xTg-AD mice. Int J Alzheimers Dis 2010:128354.  https://doi.org/10.4061/2010/128354 Google Scholar
  111. Giordano G, Tait L, Furlong CE, Cole TB, Kavanagh TJ, Costa LG (2013) Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression. Free Radic Biol Med 58:98–108.  https://doi.org/10.1016/j.freeradbiomed.2013.01.019 Google Scholar
  112. Gobinath AR, Mahmoud R, Galea LA (2014) Influence of sex and stress exposure across the lifespan on endophenotypes of depression: focus on behavior, glucocorticoids, and hippocampus. Front Neurosci 8:420.  https://doi.org/10.3389/fnins.2014.00420 Google Scholar
  113. Godar SC, Bortolato M (2014) Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission. Front Behav Neurosci 8:71.  https://doi.org/10.3389/fnbeh.2014.00071 Google Scholar
  114. Gozes I (2017) Sexual divergence in activity-dependent neuroprotective protein impacting autism, schizophrenia, and Alzheimer’s disease. J Neurosci Res 95:652–660.  https://doi.org/10.1002/jnr.23808 Google Scholar
  115. Grimm A, Mensah-Nyagan AG, Eckert A (2016a) Alzheimer, mitochondria and gender. Neurosci Biobehav Rev 67:89–101.  https://doi.org/10.1016/j.neubiorev.2016.04.012 Google Scholar
  116. Grimm SL, Hartig SM, Edwards DP (2016b) Progesterone receptor signaling mechanisms. J Mol Biol 428:3831–3849.  https://doi.org/10.1016/j.jmb.2016.06.020 Google Scholar
  117. Guarneri R et al (2004) Retinal oxidation, apoptosis and age- and sex-differences in the mnd mutant mouse, a model of neuronal ceroid lipofuscinosis. Brain Res 1014:209–220.  https://doi.org/10.1016/j.brainres.2004.04.040 Google Scholar
  118. Guevara R, Santandreu FM, Valle A, Gianotti M, Oliver J, Roca P (2009) Sex-dependent differences in aged rat brain mitochondrial function and oxidative stress. Free Radic Biol Med 46:169–175.  https://doi.org/10.1016/j.freeradbiomed.2008.09.035 Google Scholar
  119. Guevara R, Gianotti M, Oliver J, Roca P (2011) Age and sex-related changes in rat brain mitochondrial oxidative status. Exp Gerontol 46:923–928.  https://doi.org/10.1016/j.exger.2011.08.003 Google Scholar
  120. Gutierrez-Lobos K, Scherer M, Anderer P, Katschnig H (2002) The influence of age on the female/male ratio of treated incidence rates in depression. BMC Psychiatry 2:3Google Scholar
  121. Harish G, Venkateshappa C, Mahadevan A, Pruthi N, Srinivas Bharath MM, Shankar SK (2011) Glutathione metabolism is modulated by postmortem interval, gender difference and agonal state in postmortem human brains. Neurochem Int 59:1029–1042.  https://doi.org/10.1016/j.neuint.2011.08.024 Google Scholar
  122. Harish G, Venkateshappa C, Mahadevan A, Pruthi N, Srinivas Bharath MM, Shankar SK (2012) Effect of premortem and postmortem factors on the distribution and preservation of antioxidant activities in the cytosol and synaptosomes of human brains. Biopreserv Biobank 10:253–265.  https://doi.org/10.1089/bio.2012.0001 Google Scholar
  123. Harley KG, Gunier RB, Kogut K, Johnson C, Bradman A, Calafat AM, Eskenazi B (2013) Prenatal and early childhood bisphenol A concentrations and behavior in school-aged children. Environ Res 126:43–50.  https://doi.org/10.1016/j.envres.2013.06.004 Google Scholar
  124. Harvey BH, Hamer M, Louw R, van der Westhuizen FH, Malan L (2013) Metabolic and glutathione redox markers associated with brain-derived neurotrophic factor in depressed African men and women: evidence for counterregulation? Neuropsychobiology 67:33–40.  https://doi.org/10.1159/000343501 Google Scholar
  125. Hashimoto JG, Wiren KM (2008) Neurotoxic consequences of chronic alcohol withdrawal: expression profiling reveals importance of gender over withdrawal severity. Neuropsychopharmacology 33:1084–1096.  https://doi.org/10.1038/sj.npp.1301494 Google Scholar
  126. Hashimoto JG, Wiren KM, Wilhelm CJ (2016) A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy. Neurotoxicol Teratol 56:35–40.  https://doi.org/10.1016/j.ntt.2016.06.001 Google Scholar
  127. Hassoun EA, Al-Ghafri M, Abushaban A (2003) The role of antioxidant enzymes in TCDD-induced oxidative stress in various brain regions of rats after subchronic exposure. Free Radic Biol Med 35:1028–1036Google Scholar
  128. Hassoun EA, Vodhanel J, Abushaban A (2004) The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced oxidative stress in different brain regions of rats after subchronic exposure. J Biochem Mol Toxicol 18:196–203.  https://doi.org/10.1002/jbt.20030 Google Scholar
  129. Hausmann M (2017) Why sex hormones matter for neuroscience: a very short review on sex, sex hormones, and functional brain asymmetries. J Neurosci Res 95:40–49.  https://doi.org/10.1002/jnr.23857 Google Scholar
  130. Hill RA (2016) Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology. Neurosci Biobehav Rev 67:41–56.  https://doi.org/10.1016/j.neubiorev.2015.10.014 Google Scholar
  131. Hodes GE, Walker DM, Labonte B, Nestler EJ, Russo SJ (2017) Understanding the epigenetic basis of sex differences in depression. J Neurosci Res 95:692–702.  https://doi.org/10.1002/jnr.23876 Google Scholar
  132. Hu Y, Wu DL, Luo CX, Zhu LJ, Zhang J, Wu HY, Zhu DY (2012) Hippocampal nitric oxide contributes to sex difference in affective behaviors. Proc Natl Acad Sci U S A 109:14224–14229.  https://doi.org/10.1073/pnas.1207461109 Google Scholar
  133. Huang M, Liu W, Li Q, Wu CF (2002) Endogenous released ascorbic acid suppresses ethanol-induced hydroxyl radical production in rat striatum. Brain Res 944:90–96Google Scholar
  134. Hyer MM, Phillips LL, Neigh GN (2018) Sex differences in synaptic plasticity: hormones and beyond. Front Mol Neurosci 11:266.  https://doi.org/10.3389/fnmol.2018.00266 Google Scholar
  135. Ilzecka J (2003) Total antioxidant status is increased in the serum of amyotrophic lateral sclerosis patients. Scand J Clin Lab Invest 63:297–302Google Scholar
  136. Irwin RW, Yao J, Hamilton RT, Cadenas E, Brinton RD, Nilsen J (2008) Progesterone and estrogen regulate oxidative metabolism in brain mitochondria. Endocrinology 149:3167–3175.  https://doi.org/10.1210/en.2007-1227 Google Scholar
  137. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39:73–82.  https://doi.org/10.1080/01616412.2016.1251711 Google Scholar
  138. Iwasaki Y, Ikeda K, Kinoshita M (1995) Vitamin A and E levels are normal in amyotrophic lateral sclerosis. J Neurol Sci 132:193–194Google Scholar
  139. Jaber SM, Bordt EA, Bhatt NM, Lewis DM, Gerecht S, Fiskum G, Polster BM (2017) Sex differences in the mitochondrial bioenergetics of astrocytes but not microglia at a physiologically relevant brain oxygen tension. Neurochem Int.  https://doi.org/10.1016/j.neuint.2017.09.003
  140. Jazin E, Cahill L (2010) Sex differences in molecular neuroscience: from fruit flies to humans. Nat Rev Neurosci 11:9–17.  https://doi.org/10.1038/nrn2754 Google Scholar
  141. Jung ME, Metzger DB (2016) A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats. Behav Brain Res 314:199–214.  https://doi.org/10.1016/j.bbr.2016.07.054 Google Scholar
  142. Kabuto H, Hasuike S, Minagawa N, Shishibori T (2003) Effects of bisphenol A on the metabolisms of active oxygen species in mouse tissues. Environ Res 93:31–35Google Scholar
  143. Kaczkurkin AN, Raznahan A, Satterthwaite TD (2018) Sex differences in the developing brain: insights from multimodal neuroimaging. Neuropsychopharmacology.  https://doi.org/10.1038/s41386-018-0111-z
  144. Kalaitzidis D, Gilmore TD (2005) Transcription factor cross-talk: the estrogen receptor and NF-kappaB. Trends Endocrinol Metab 16:46–52.  https://doi.org/10.1016/j.tem.2005.01.004 Google Scholar
  145. Kalinina EV, Chernov NN, Novichkova MD (2014) Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes. Biochemistry Biokhimiia 79:1562–1583.  https://doi.org/10.1134/s0006297914130082 Google Scholar
  146. Kamper EF, Chatzigeorgiou A, Tsimpoukidi O, Kamper M, Dalla C, Pitychoutis PM, Papadopoulou-Daifoti Z (2009) Sex differences in oxidant/antioxidant balance under a chronic mild stress regime. Physiol Behav 98:215–222.  https://doi.org/10.1016/j.physbeh.2009.05.011 Google Scholar
  147. Kant L, Yilmaz O, Taskiran D, Kulali B, Furedy JJ, Demirgoren S, Pogun S (2000) Sexually dimorphic cognitive style, female sex hormones, and cortical nitric oxide. Physiol Behav 71:277–287Google Scholar
  148. Katalinic V, Modun D, Music I, Boban M (2005) Gender differences in antioxidant capacity of rat tissues determined by 2,2'-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. Comp Biochem Physiol Toxicol Pharmacol 140:47–52.  https://doi.org/10.1016/j.cca.2005.01.005 Google Scholar
  149. Kaye W (2008) Neurobiology of anorexia and bulimia nervosa. Physiol Behav 94:121–135.  https://doi.org/10.1016/j.physbeh.2007.11.037 Google Scholar
  150. Keizman D et al (2009) Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress? J Neurol Sci 285:95–99.  https://doi.org/10.1016/j.jns.2009.06.002 Google Scholar
  151. Kenchappa RS, Diwakar L, Annepu J, Ravindranath V (2004) Estrogen and neuroprotection: higher constitutive expression of glutaredoxin in female mice offers protection against MPTP-mediated neurodegeneration. FASEB J 18:1102–1104.  https://doi.org/10.1096/fj.03-1075fje Google Scholar
  152. Khaksari M, Soltani Z, Shahrokhi N (2017) Effects of female sex steroids administration on pathophysiologic mechanisms in traumatic brain injury. Transl Stroke Res.  https://doi.org/10.1007/s12975-017-0588-5
  153. Khalifa AR et al (2017) Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ROS homeostasis in young mouse heart and brain. Physiol Rep 5.  https://doi.org/10.14814/phy2.13125
  154. Khan A, Harney JW, Zavacki AM, Sajdel-Sulkowska EM (2014) Disrupted brain thyroid hormone homeostasis and altered thyroid hormone-dependent brain gene expression in autism spectrum disorders. J Physiol Pharmacol 65:257–272Google Scholar
  155. Kirkman HN, Gaetani GF (2007) Mammalian catalase: a venerable enzyme with new mysteries. Trends Biochem Sci 32:44–50.  https://doi.org/10.1016/j.tibs.2006.11.003 Google Scholar
  156. Kleinert H, Schwarz PM, Forstermann U (2003) Regulation of the expression of inducible nitric oxide synthase. Biol Chem 384:1343–1364.  https://doi.org/10.1515/bc.2003.152 Google Scholar
  157. Klepac N, Relja M, Klepac R, Hecimovic S, Babic T, Trkulja V (2007) Oxidative stress parameters in plasma of Huntington’s disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects : a cross-sectional study. J Neurol 254:1676–1683.  https://doi.org/10.1007/s00415-007-0611-y Google Scholar
  158. Knight TR, Choudhuri S, Klaassen CD (2007) Constitutive mRNA expression of various glutathione S-transferase isoforms in different tissues of mice. Toxicol Sci 100:513–524.  https://doi.org/10.1093/toxsci/kfm233 Google Scholar
  159. Krementsov DN, Asarian L, Fang QM, McGill MM, Teuscher C (2018) Sex-specific gene-by-vitamin D interactions regulate susceptibility to central nervous system autoimmunity. Front Immunol 9:1622Google Scholar
  160. Krolow R, Noschang CG, Arcego D, Andreazza AC, Peres W, Goncalves CA, Dalmaz C (2010) Consumption of a palatable diet by chronically stressed rats prevents effects on anxiety-like behavior but increases oxidative stress in a sex-specific manner. Appetite 55:108–116.  https://doi.org/10.1016/j.appet.2010.03.013 Google Scholar
  161. Kume-Kick J, Rice ME (1998) Estrogen-dependent modulation of rat brain ascorbate levels and ischemia-induced ascorbate loss. Brain Res 803:105–113Google Scholar
  162. Kume-Kick J, Ferris DC, Russo-Menna I, Rice ME (1996) Enhanced oxidative stress in female rat brain after gonadectomy. Brain Res 738:8–14Google Scholar
  163. Kushleika J, Checkoway H, Woods JS, Moon JD, Smith-Weller T, Franklin GM, Swanson PD (1996) Selegiline and lymphocyte superoxide dismutase activities in Parkinson’s disease. Ann Neurol 39:378–381.  https://doi.org/10.1002/ana.410390315 Google Scholar
  164. Kushner PJ, Agard DA, Greene GL, Scanlan TS, Shiau AK, Uht RM, Webb P (2000) Estrogen receptor pathways to AP-1. J Steroid Biochem Mol Biol 74:311–317Google Scholar
  165. Labandeira-Garcia JL, Rodriguez-Perez AI, Valenzuela R, Costa-Besada MA, Guerra MJ (2016) Menopause and Parkinson’s disease. Interaction between estrogens and brain renin-angiotensin system in dopaminergic degeneration. Front Neuroendocrinol 43:44–59.  https://doi.org/10.1016/j.yfrne.2016.09.003 Google Scholar
  166. Lapidus KA, Gabbay V, Mao X, Johnson A, Murrough JW, Mathew SJ, Shungu DC (2014) In vivo (1)H MRS study of potential associations between glutathione, oxidative stress and anhedonia in major depressive disorder. Neurosci Lett 569:74–79.  https://doi.org/10.1016/j.neulet.2014.03.056 Google Scholar
  167. Lazarus RC, Buonora JE, Jacobowitz DM, Mueller GP (2015) Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences. Free Radic Biol Med 78:89–100.  https://doi.org/10.1016/j.freeradbiomed.2014.10.507 Google Scholar
  168. Lee SY, Andoh T, Murphy DL, Chiueh CC (2003) 17beta-estradiol activates ICI 182,780-sensitive estrogen receptors and cyclic GMP-dependent thioredoxin expression for neuroprotection. FASEB J 17:947–948.  https://doi.org/10.1096/fj.02-0807fje Google Scholar
  169. Leger M, Neill JC (2016) A systematic review comparing sex differences in cognitive function in schizophrenia and in rodent models for schizophrenia, implications for improved therapeutic strategies. Neurosci Biobehav Rev 68:979–1000.  https://doi.org/10.1016/j.neubiorev.2016.06.029 Google Scholar
  170. Li G, Sang N, Wang Q (2006) Oxidative damage induced in brains and livers of mice by landfill leachate. Ecotoxicol Environ Saf 65:134–139.  https://doi.org/10.1016/j.ecoenv.2005.06.011 Google Scholar
  171. Li R, Strykowski R, Meyer M, Mulcrone P, Krakora D, Suzuki M (2012) Male-specific differences in proliferation, neurogenesis, and sensitivity to oxidative stress in neural progenitor cells derived from a rat model of ALS. PLoS One 7:e48581.  https://doi.org/10.1371/journal.pone.0048581 Google Scholar
  172. Li L, Chen J, Sun S, Zhao J, Dong X, Wang J (2017) Effects of estradiol on autophagy and Nrf-2/ARE signals after cerebral ischemia. Cell Physiol Biochem 41:2027–2036.  https://doi.org/10.1159/000475433 Google Scholar
  173. Lilienthal H, Verwer CM, van der Ven LT, Piersma AH, Vos JG (2008) Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology 246:45–54.  https://doi.org/10.1016/j.tox.2008.01.007 Google Scholar
  174. Liu H, Harrell LE, Shenvi S, Hagen T, Liu RM (2005) Gender differences in glutathione metabolism in Alzheimer’s disease. J Neurosci Res 79:861–867.  https://doi.org/10.1002/jnr.20424 Google Scholar
  175. Liu L et al (2009) A comparative study on oxidative damage and distributions of perfluorooctane sulfonate (PFOS) in mice at different postnatal developmental stages. J Toxicol Sci 34:245–254Google Scholar
  176. Liu M, Kelley MH, Herson PS, Hurn PD (2010) Neuroprotection of sex steroids. Minerva Endocrinol 35:127–143Google Scholar
  177. Liu T, Zhong S, Liao X, Chen J, He T, Lai S, Jia Y (2015) A meta-analysis of oxidative stress markers in depression. PLoS One 10:e0138904.  https://doi.org/10.1371/journal.pone.0138904 Google Scholar
  178. Llop S, Lopez-Espinosa MJ, Rebagliato M, Ballester F (2013) Gender differences in the neurotoxicity of metals in children. Toxicology 311:3–12.  https://doi.org/10.1016/j.tox.2013.04.015 Google Scholar
  179. Lloret A et al (2008) Gender and age-dependent differences in the mitochondrial apoptogenic pathway in Alzheimer’s disease. Free Radic Biol Med 44:2019–2025.  https://doi.org/10.1016/j.freeradbiomed.2008.02.017 Google Scholar
  180. Loke H, Harley V, Lee J (2015) Biological factors underlying sex differences in neurological disorders. Int J Biochem Cell Biol 65:139–150.  https://doi.org/10.1016/j.biocel.2015.05.024 Google Scholar
  181. Lu J, Holmgren A (2014) The thioredoxin antioxidant system. Free Radic Biol Med 66:75–87.  https://doi.org/10.1016/j.freeradbiomed.2013.07.036 Google Scholar
  182. Luders E, Toga AW (2010) Sex differences in brain anatomy. Prog Brain Res 186:3–12.  https://doi.org/10.1016/b978-0-444-53630-3.00001-4 Google Scholar
  183. Malagutti KS et al (2009) 17beta-estradiol decreases methylmercury-induced neurotoxicity in male mice. Environ Toxicol Pharmacol 27:293–297.  https://doi.org/10.1016/j.etap.2008.11.005 Google Scholar
  184. Marino M, Galluzzo P, Ascenzi P (2006) Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics 7:497–508Google Scholar
  185. Maris AF et al (2010) Gender effects of acute malathion or zinc exposure on the antioxidant response of rat hippocampus and cerebral cortex. Basic Clin Pharmacol Toxicol 107:965–970.  https://doi.org/10.1111/j.1742-7843.2010.00614.x Google Scholar
  186. Marks AR et al (2010) Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study. Environ Health Perspect 118:1768–1774.  https://doi.org/10.1289/ehp.1002056 Google Scholar
  187. Marmol F, Rodriguez CA, Sanchez J, Chamizo VD (2015) Anti-oxidative effects produced by environmental enrichment in the hippocampus and cerebral cortex of male and female rats. Brain Res 1613:120–129.  https://doi.org/10.1016/j.brainres.2015.04.007 Google Scholar
  188. McCarthy MM, Pickett LA, VanRyzin JW, Kight KE (2015) Surprising origins of sex differences in the brain. Horm Behav 76:3–10.  https://doi.org/10.1016/j.yhbeh.2015.04.013 Google Scholar
  189. McCombe PA, Henderson RD (2010) Effects of gender in amyotrophic lateral sclerosis. Gend Med 7:557–570.  https://doi.org/10.1016/j.genm.2010.11.010 Google Scholar
  190. McCullough LD, Zeng Z, Blizzard KK, Debchoudhury I, Hurn PD (2005) Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection. J Cereb Blood Flow Metab 25:502–512.  https://doi.org/10.1038/sj.jcbfm.9600059 Google Scholar
  191. McEwen BS, Milner TA (2017) Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res 95:24–39.  https://doi.org/10.1002/jnr.23809 Google Scholar
  192. McFarland NR, Burdett T, Desjardins CA, Frosch MP, Schwarzschild MA (2013) Postmortem brain levels of urate and precursors in Parkinson's disease and related disorders. Neurodegener Dis 12:189–198.  https://doi.org/10.1159/000346370 Google Scholar
  193. Mendrek A, Mancini-Marie A (2016) Sex/gender differences in the brain and cognition in schizophrenia. Neurosci Biobehav Rev 67:57–78.  https://doi.org/10.1016/j.neubiorev.2015.10.013 Google Scholar
  194. Merlo S, Spampinato SF, Sortino MA (2017) Estrogen and Alzheimer’s disease: still an attractive topic despite disappointment from early clinical results. Eur J Pharmacol.  https://doi.org/10.1016/j.ejphar.2017.05.059
  195. Mhaouty-Kodja S (2018) Role of the androgen receptor in the central nervous system. Mol Cell Endocrinol 465:103–112.  https://doi.org/10.1016/j.mce.2017.08.001 Google Scholar
  196. Mishra VN et al (2014) Lathyrism: has the scenario changed in 2013? Neurol Res 36:38–40.  https://doi.org/10.1179/1743132813y.0000000258 Google Scholar
  197. Misiak M, Beyer C, Arnold S (2010) Gender-specific role of mitochondria in the vulnerability of 6-hydroxydopamine-treated mesencephalic neurons. Biochim Biophys Acta 1797:1178–1188.  https://doi.org/10.1016/j.bbabio.2010.04.009 Google Scholar
  198. Mitchell AE, Morin D, Lakritz J, Jones AD (1997) Quantitative profiling of tissue- and gender-related expression of glutathione S-transferase isoenzymes in the mouse. Biochem J 325(Pt 1):207–216Google Scholar
  199. Mitchell J, Morris A, de Belleroche J (2009) Thioredoxin reductase 1 haplotypes modify familial amyotrophic lateral sclerosis onset. Free Radic Biol Med 46:202–211.  https://doi.org/10.1016/j.freeradbiomed.2008.09.041 Google Scholar
  200. Mohagheghi F, Khalaj L, Ahmadiani A, Rahmani B (2013) Gemfibrozil pretreatment affecting antioxidant defense system and inflammatory, but not Nrf-2 signaling pathways resulted in female neuroprotection and male neurotoxicity in the rat models of global cerebral ischemia-reperfusion. Neurotox Res 23:225–237.  https://doi.org/10.1007/s12640-012-9338-3 Google Scholar
  201. Mokhtari Z, Hekmatdoost A, Nourian M (2017) Antioxidant efficacy of vitamin D. J Parathyr Dis 5:11–16Google Scholar
  202. Monte AS et al (2017) Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: study of sex differences and brain oxidative alterations. Behav Brain Res 331:30–37.  https://doi.org/10.1016/j.bbr.2017.04.057 Google Scholar
  203. Moorthy K, Sharma D, Basir SF, Baquer NZ (2005) Administration of estradiol and progesterone modulate the activities of antioxidant enzyme and aminotransferases in naturally menopausal rats. Exp Gerontol 40:295–302.  https://doi.org/10.1016/j.exger.2005.01.004 Google Scholar
  204. Moreira AC, Silva AM, Santos MS, Sardao VA (2013) Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: investigation of the role of gender. Food Chem Toxicol 53:18–26.  https://doi.org/10.1016/j.fct.2012.11.031 Google Scholar
  205. Moretti R, Morelli ME, Caruso P (2018) Vitamin D in neurological diseases: a rationale for a pathogenic impact. Int J Mol Sci 19.  https://doi.org/10.3390/ijms19082245
  206. Nelson LH, Saulsbery AI, Lenz KM (2018) Small cells with big implications: microglia and sex differences in brain development, plasticity and behavioral health. Prog Neurobiol.  https://doi.org/10.1016/j.pneurobio.2018.09.002
  207. Netto CA, Sanches E, Odorcyk FK, Duran-Carabali LE, Weis SN (2017) Sex-dependent consequences of neonatal brain hypoxia-ischemia in the rat. J Neurosci Res 95:409–421.  https://doi.org/10.1002/jnr.23828 Google Scholar
  208. Ngun TC, Ghahramani N, Sanchez FJ, Bocklandt S, Vilain E (2011) The genetics of sex differences in brain and behavior. Front Neuroendocrinol 32:227–246.  https://doi.org/10.1016/j.yfrne.2010.10.001 Google Scholar
  209. Noschang CG et al (2010) Neonatal handling impairs spatial memory and leads to altered nitric oxide production and DNA breaks in a sex specific manner. Neurochem Res 35:1083–1091.  https://doi.org/10.1007/s11064-010-0158-7 Google Scholar
  210. Noschang C, Krolow R, Arcego DM, Toniazzo AP, Huffell AP, Dalmaz C (2012) Neonatal handling affects learning, reversal learning and antioxidant enzymes activities in a sex-specific manner in rats. Int J Dev Neurosci 30:285–291.  https://doi.org/10.1016/j.ijdevneu.2012.01.010 Google Scholar
  211. Oh SI, Baek S, Park JS, Piao L, Oh KW, Kim SH (2015) Prognostic role of serum levels of uric acid in amyotrophic lateral sclerosis. J Clin Neurol 11, 376:–382.  https://doi.org/10.3988/jcn.2015.11.4.376
  212. Onishchenko N, Fischer C, Wan Ibrahim WN, Negri S, Spulber S, Cottica D, Ceccatelli S (2011) Prenatal exposure to PFOS or PFOA alters motor function in mice in a sex-related manner. Neurotox Res 19:452–461.  https://doi.org/10.1007/s12640-010-9200-4 Google Scholar
  213. Osborne BF, Turano A, Schwarz JM (2018) Sex differences in the neuroimmune system. Curr Opin Behav Sci 23:118–123.  https://doi.org/10.1016/j.cobeha.2018.05.007 Google Scholar
  214. Oskarsson B, Horton DK, Mitsumoto H (2015) Potential environmental factors in amyotrophic lateral sclerosis. Neurol Clin 33:877–888.  https://doi.org/10.1016/j.ncl.2015.07.009 Google Scholar
  215. Pajovic SB, Saicic ZS (2008) Modulation of antioxidant enzyme activities by sexual steroid hormones. Physiol Res 57:801–811Google Scholar
  216. Pajovic S, Nikezic G, Martinovic JV (1993) Effects of ovarian steroids on superoxide dismutase activity in the rat brain. Experientia 49:73–75Google Scholar
  217. Pajovic SB, Saicic ZS, Spasic MB, Petrovic VM (2003) The effect of ovarian hormones on antioxidant enzyme activities in the brain of male rats. Physiol Res 52:189–194Google Scholar
  218. Palanza P, Nagel SC, Parmigiani S, Vom Saal FS (2016) Perinatal exposure to endocrine disruptors: sex, timing and behavioral endpoints. Curr Opin Behav Sci 7:69–75.  https://doi.org/10.1016/j.cobeha.2015.11.017 Google Scholar
  219. Park EM et al (2006) Inducible nitric oxide synthase contributes to gender differences in ischemic brain injury. J Cereb Blood Flow Metab 26:392–401.  https://doi.org/10.1038/sj.jcbfm.9600194 Google Scholar
  220. Pejic S, Kasapovic J, Cvetkovic D, Pajovic SB (2003) The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain. Braz J Med Biol Res Revista Brasileira de Pesquisas Medicas e Biologicas 36:579–586Google Scholar
  221. Pekmezovic T et al (2007) Survival of Huntington’s disease patients in Serbia: longer survival in female patients. Eur J Epidemiol 22:523–526.  https://doi.org/10.1007/s10654-007-9157-7 Google Scholar
  222. Peskind ER et al (2014) Influence of lifestyle modifications on age-related free radical injury to brain. JAMA Neurol 71:1150–1154.  https://doi.org/10.1001/jamaneurol.2014.1428 Google Scholar
  223. Peternel S, Pilipovic K, Zupan G (2009) Seizure susceptibility and the brain regional sensitivity to oxidative stress in male and female rats in the lithium-pilocarpine model of temporal lobe epilepsy. Prog Neuro-Psychopharmacol Biol Psychiatry 33:456–462.  https://doi.org/10.1016/j.pnpbp.2009.01.005 Google Scholar
  224. Picillo M, Nicoletti A, Fetoni V, Garavaglia B, Barone P, Pellecchia MT (2017) The relevance of gender in Parkinson's disease: a review. J Neurol 264:1583–1607.  https://doi.org/10.1007/s00415-016-8384-9 Google Scholar
  225. Pike CJ (2017) Sex and the development of Alzheimer’s disease. J Neurosci Res 95:671–680.  https://doi.org/10.1002/jnr.23827 Google Scholar
  226. Pinares-Garcia P, Stratikopoulos M, Zagato A, Loke H, Lee J (2018) Sex: a significant risk factor for neurodevelopmental and neurodegenerative disorders. Brain Sci:8.  https://doi.org/10.3390/brainsci8080154
  227. Podcasy JL, Epperson CN (2016) Considering sex and gender in Alzheimer disease and other dementias. Dialogues Clin Neurosci 18:437–446Google Scholar
  228. Pohjanvirta R, Unkila M, Tuomisto J (1993) Comparative acute lethality of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin in the most TCDD-susceptible and the most TCDD-resistant rat strain. Pharmacol Toxicol 73:52–56Google Scholar
  229. Pohjanvirta R, Miettinen H, Sankari S, Hegde N, Linden J (2012) Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice. Toxicol Appl Pharmacol 262:167–176.  https://doi.org/10.1016/j.taap.2012.04.032 Google Scholar
  230. Preciados M, Yoo C, Roy D (2016) Estrogenic endocrine disrupting chemicals influencing NRF1 regulated gene networks in the development of complex human brain diseases. Int J Mol Sci 17.  https://doi.org/10.3390/ijms17122086
  231. Quillinan N, Deng G, Grewal H, Herson PS (2014) Androgens and stroke: good, bad or indifferent? Exp Neurol 259:10–15.  https://doi.org/10.1016/j.expneurol.2014.02.004 Google Scholar
  232. Ramos-Chavez LA, Rendon-Lopez CR, Zepeda A, Silva-Adaya D, Del Razo LM, Gonsebatt ME (2015) Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. Front Cell Neurosci 9:21.  https://doi.org/10.3389/fncel.2015.00021 Google Scholar
  233. Ratnu VS, Emami MR, Bredy TW (2017) Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain. J Neurosci Res 95:301–310.  https://doi.org/10.1002/jnr.23886 Google Scholar
  234. Rauchova H, Vokurkova M, Koudelova J (2012) Hypoxia-induced lipid peroxidation in the brain during postnatal ontogenesis. Physiol Res 61(Suppl 1):S89–S101Google Scholar
  235. Razmara A, Duckles SP, Krause DN, Procaccio V (2007) Estrogen suppresses brain mitochondrial oxidative stress in female and male rats. Brain Res 1176:71–81.  https://doi.org/10.1016/j.brainres.2007.08.036 Google Scholar
  236. Rebuli ME, Patisaul HB (2016) Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain. J Steroid Biochem Mol Biol 160:148–159.  https://doi.org/10.1016/j.jsbmb.2015.08.021 Google Scholar
  237. Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 1863:2977–2992.  https://doi.org/10.1016/j.bbamcr.2016.09.012 Google Scholar
  238. Reilly MP, Weeks CD, Topper VY, Thompson LM, Crews D, Gore AC (2015) The effects of prenatal PCBs on adult social behavior in rats. Horm Behav 73:47–55.  https://doi.org/10.1016/j.yhbeh.2015.06.002 Google Scholar
  239. Ren J (2007) Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 34:432–438.  https://doi.org/10.1111/j.1440-1681.2007.04591.x Google Scholar
  240. Ren X et al (2017) Redox signaling mediated by Thioredoxin and glutathione Systems in the Central Nervous System. Antioxid Redox Signal 27:989–1010.  https://doi.org/10.1089/ars.2016.6925 Google Scholar
  241. Robberecht W et al (1994) Cu/Zn superoxide dismutase activity in familial and sporadic amyotrophic lateral sclerosis. J Neurochem 62:384–387Google Scholar
  242. Robertson CL, Saraswati M (2015) Progesterone protects mitochondrial function in a rat model of pediatric traumatic brain injury. J Bioenerg Biomembr 47:43–51.  https://doi.org/10.1007/s10863-014-9585-5 Google Scholar
  243. Roof RL, Hall ED (2000) Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. J Neurotrauma 17:367–388.  https://doi.org/10.1089/neu.2000.17.367 Google Scholar
  244. Roos RA, Vegter-van der Vlis M, Hermans J, Elshove HM, Moll AC, van de Kamp JJ, Bruyn GW (1991) Age at onset in Huntington's disease: effect of line of inheritance and patient’s sex. J Med Genet 28:515–519Google Scholar
  245. Russwurm M, Russwurm C, Koesling D, Mergia E (2013) NO/cGMP: the past, the present, and the future. Methods Mol Biol (Clifton, NJ) 1020:1–16.  https://doi.org/10.1007/978-1-62703-459-3_1 Google Scholar
  246. Ruszkiewicz J, Albrecht J (2015) Changes in the mitochondrial antioxidant systems in neurodegenerative diseases and acute brain disorders. Neurochem Int 88:66–72.  https://doi.org/10.1016/j.neuint.2014.12.012 Google Scholar
  247. Ruszkiewicz JA, Bowman AB, Farina M, Rocha JBT, Aschner M (2016) Sex- and structure-specific differences in antioxidant responses to methylmercury during early development. Neurotoxicology 56:118–126.  https://doi.org/10.1016/j.neuro.2016.07.009 Google Scholar
  248. Rutkai I, Dutta S, Katakam PV, Busija DW (2015) Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries. Am J Phys Heart Circ Phys 309:H1490–H1500.  https://doi.org/10.1152/ajpheart.00231.2015 Google Scholar
  249. Sadowski RN, Wise LM, Park PY, Schantz SL, Juraska JM (2014) Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females. Neuroscience 279:122–131.  https://doi.org/10.1016/j.neuroscience.2014.08.038 Google Scholar
  250. Saeed U et al (2009) Redox activated MAP kinase death signaling cascade initiated by ASK1 is not activated in female mice following MPTP: novel mechanism of neuroprotection. Neurotox Res 16:116–126.  https://doi.org/10.1007/s12640-009-9058-5 Google Scholar
  251. Saicic ZS, Pajovic SB, Korac B, Spasic MB, Martinovic JV, Petrovic VM (1998) Glutathione-dependent antioxidant enzyme activities and glutathione content in the rat brain at different stages of oestrous cycle. Physiol Res 47:61–67Google Scholar
  252. Salim S (2017) Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360:201–205.  https://doi.org/10.1124/jpet.116.237503 Google Scholar
  253. Sampei K et al (2000) Stroke outcome in double-mutant antioxidant transgenic mice. Stroke 31:2685–2691Google Scholar
  254. Santa Maria C, Machado A (1986) Age and sex related differences in some rat renal NADPH-consuming detoxification enzymes. Arch Gerontol Geriatr 5:235–247Google Scholar
  255. Schmidt AJ, Krieg J, Vedder H (2002) Differential effects of glucocorticoids and gonadal steroids on glutathione levels in neuronal and glial cell systems. J Neurosci Res 67:544–550.  https://doi.org/10.1002/jnr.10146 Google Scholar
  256. Schuessel K, Leutner S, Cairns NJ, Muller WE, Eckert A (2004) Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer’s disease brain. J Neural Transm (Vienna, Austria: 1996) 111:1167–1182.  https://doi.org/10.1007/s00702-004-0156-5 Google Scholar
  257. Schuessel K et al (2005) Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol Dis 18:89–99.  https://doi.org/10.1016/j.nbd.2004.09.003 Google Scholar
  258. Selvakumar K, Bavithra S, Ganesh L, Krishnamoorthy G, Venkataraman P, Arunakaran J (2013) Polychlorinated biphenyls induced oxidative stress mediated neurodegeneration in hippocampus and behavioral changes of adult rats: anxiolytic-like effects of quercetin. Toxicol Lett 222:45–54.  https://doi.org/10.1016/j.toxlet.2013.06.237 Google Scholar
  259. Shahrokhi N, Haddad MK, Joukar S, Shabani M, Keshavarzi Z, Shahozehi B (2012) Neuroprotective antioxidant effect of sex steroid hormones in traumatic brain injury. Pak J Pharm Sci 25:219–225Google Scholar
  260. Shumaker SA et al (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative memory study: a randomized controlled trial. JAMA 289:2651–2662.  https://doi.org/10.1001/jama.289.20.2651 Google Scholar
  261. Siddiqui AN et al (2016) Neuroprotective role of steroidal sex hormones: an overview. CNS Neurosci Ther 22:342–350.  https://doi.org/10.1111/cns.12538 Google Scholar
  262. Silva TLA et al (2018) Serotonin transporter inhibition during neonatal period induces sex-dependent effects on mitochondrial bioenergetics in the rat brainstem. Eur J Neurosci.  https://doi.org/10.1111/ejn.13971
  263. Silva-Adaya D, Gonsebatt ME, Guevara J (2014) Thioredoxin system regulation in the central nervous system: experimental models and clinical evidence. Oxidative Med Cell Longev 2014:590808.  https://doi.org/10.1155/2014/590808 Google Scholar
  264. Singh G, Singh V, Sobolewski M, Cory-Slechta DA, Schneider JS (2018) Sex-dependent effects of developmental lead exposure on the brain. Front Genet 9:89.  https://doi.org/10.3389/fgene.2018.00089 Google Scholar
  265. Smaga I et al (2015) Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacol Rep 67:569–580.  https://doi.org/10.1016/j.pharep.2014.12.015 Google Scholar
  266. Smith KM, Dahodwala N (2014) Sex differences in Parkinson’s disease and other movement disorders. Exp Neurol 259:44–56.  https://doi.org/10.1016/j.expneurol.2014.03.010 Google Scholar
  267. Smith AL, Alexander M, Rosenkrantz TS, Sadek ML, Fitch RH (2014) Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury. Exp Neurol 254:54–67.  https://doi.org/10.1016/j.expneurol.2014.01.003 Google Scholar
  268. Sobocanec S, Balog T, Sverko V, Marotti T (2003) Sex-dependent antioxidant enzyme activities and lipid peroxidation in ageing mouse brain. Free Radic Res 37:743–748Google Scholar
  269. Sobocanec S, Balog T, Kusic B, Sverko V, Saric A, Marotti T (2008) Differential response to lipid peroxidation in male and female mice with age: correlation of antioxidant enzymes matters. Biogerontology 9:335–343.  https://doi.org/10.1007/s10522-008-9145-7 Google Scholar
  270. Sobolewski M, Conrad K, Allen JL, Weston H, Martin K, Lawrence BP, Cory-Slechta DA (2014) Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals. Neurotoxicology 45:121–130.  https://doi.org/10.1016/j.neuro.2014.09.008 Google Scholar
  271. Son SW, Lee JS, Kim HG, Kim DW, Ahn YC, Son CG (2016) Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model. J Neurochem 136:106–117.  https://doi.org/10.1111/jnc.13371 Google Scholar
  272. Spani CB, Braun DJ, Van Eldik LJ (2018) Sex-related responses after traumatic brain injury: considerations for preclinical modeling. Front Neuroendocrinol.  https://doi.org/10.1016/j.yfrne.2018.03.006
  273. Spence RD, Voskuhl RR (2012) Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 33:105–115.  https://doi.org/10.1016/j.yfrne.2011.12.001 Google Scholar
  274. Spychala MS, Honarpisheh P, McCullough LD (2017) Sex differences in neuroinflammation and neuroprotection in ischemic stroke. J Neurosci Res 95:462–471.  https://doi.org/10.1002/jnr.23962 Google Scholar
  275. Steenkamp LR et al (2017) Severity of anxiety- but not depression- is associated with oxidative stress in major depressive disorder. J Affect Disord 219:193–200.  https://doi.org/10.1016/j.jad.2017.04.042 Google Scholar
  276. Subramanian M, Pusphendran CK, Tarachand U, Devasagayam TP (1993) Gestation confers temporary resistance to peroxidation in the maternal rat brain. Neurosci Lett 155:151–154Google Scholar
  277. Sundar Boyalla S, Barbara Victor M, Roemgens A, Beyer C, Arnold S (2011) Sex- and brain region-specific role of cytochrome c oxidase in 1-methyl-4-phenylpyridinium-mediated astrocyte vulnerability. J Neurosci Res 89:2068–2082.  https://doi.org/10.1002/jnr.22669 Google Scholar
  278. Suszynska-Zajczyk J, Luczak M, Marczak L, Jakubowski H (2014) Inactivation of the paraoxonase 1 gene affects the expression of mouse brain proteins involved in neurodegeneration. J Alzheimers Dis 42:247–260.  https://doi.org/10.3233/jad-132714 Google Scholar
  279. Suzuki M et al (2007) Sexual dimorphism in disease onset and progression of a rat model of ALS. Amyotroph Lateral Scler 8:20–25.  https://doi.org/10.1080/17482960600982447 Google Scholar
  280. Swan SH et al (2010) Prenatal phthalate exposure and reduced masculine play in boys. Int J Androl 33:259–269.  https://doi.org/10.1111/j.1365-2605.2009.01019.x Google Scholar
  281. Taskiran D, Kutay FZ, Sozmen E, Pogun S (1997) Sex differences in nitrite/nitrate levels and antioxidant defense in rat brain. Neuroreport 8:881–884Google Scholar
  282. Taskiran D, Sagduyu A, Yuceyar N, Kutay FZ, Pogun S (2000) Increased cerebrospinal fluid and serum nitrite and nitrate levels in amyotrophic lateral sclerosis. Int J Neurosci 101:65–72Google Scholar
  283. Taylor MD, Erikson KM, Dobson AW, Fitsanakis VA, Dorman DC, Aschner M (2006) Effects of inhaled manganese on biomarkers of oxidative stress in the rat brain. Neurotoxicology 27:788–797.  https://doi.org/10.1016/j.neuro.2006.05.006 Google Scholar
  284. Thibaut F (2016) The role of sex and gender in neuropsychiatric disorders. Dialogues Clin Neurosci 18:351–352Google Scholar
  285. Thrift AG, Geoffrey DA, McNeil JJ (1995) Epidemiology of intracerebral hemorrhage. Epidemiol Rev 17:361–381Google Scholar
  286. Tobino K et al (2015) Gender- and disease-specific urinary thioredoxin in chronic kidney disease patients with or without type 2 diabetic nephropathy. Nephrology (Carlton, Vic) 20:368–374.  https://doi.org/10.1111/nep.12403 Google Scholar
  287. Tolins M, Ruchirawat M, Landrigan P (2014) The developmental neurotoxicity of arsenic: cognitive and behavioral consequences of early life exposure. Ann Glob Health 80:303–314.  https://doi.org/10.1016/j.aogh.2014.09.005 Google Scholar
  288. Torres-Rojas C, Jones BC (2018) Sex differences in neurotoxicogenetics. Front Genet 9:196.  https://doi.org/10.3389/fgene.2018.00196 Google Scholar
  289. Tyler CR, Allan AM (2014) The effects of arsenic exposure on neurological and cognitive dysfunction in human and rodent studies: a review. Curr Environ Health Rep 1:132–147.  https://doi.org/10.1007/s40572-014-0012-1 Google Scholar
  290. Uzun H, Kayali R, Cakatay U (2010) The chance of gender dependency of oxidation of brain proteins in aged rats. Arch Gerontol Geriatr 50:16–19.  https://doi.org/10.1016/j.archger.2009.01.002 Google Scholar
  291. Valentino RJ, Bangasser DA (2016) Sex-biased cellular signaling: molecular basis for sex differences in neuropsychiatric diseases. Dialogues Clin Neurosci 18:385–393Google Scholar
  292. Varshney M, Nalvarte I (2017) Genes, gender, environment, and novel functions of estrogen receptor beta in the susceptibility to neurodevelopmental disorders. Brain Sci 7.  https://doi.org/10.3390/brainsci7030024
  293. Vedder H, Anthes N, Stumm G, Wurz C, Behl C, Krieg JC (1999) Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. J Neurochem 72:2531–2538Google Scholar
  294. Velarde MC (2014) Mitochondrial and sex steroid hormone crosstalk during aging. Longev Healthspan 3:2.  https://doi.org/10.1186/2046-2395-3-2 Google Scholar
  295. Venditti P, Di Stefano L, Di Meo S (2013) Mitochondrial metabolism of reactive oxygen species. Mitochondrion 13:71–82.  https://doi.org/10.1016/j.mito.2013.01.008 Google Scholar
  296. Vignini A et al (2013) Impact of gender on platelet membrane functions of Alzheimer’s disease patients. Exp Gerontol 48:319–325.  https://doi.org/10.1016/j.exger.2012.11.015 Google Scholar
  297. Wagner AK, Bayir H, Ren D, Puccio A, Zafonte RD, Kochanek PM (2004) Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia. J Neurotrauma 21:125–136.  https://doi.org/10.1089/089771504322778596 Google Scholar
  298. Wang H, Liu H, Liu RM (2003) Gender difference in glutathione metabolism during aging in mice. Exp Gerontol 38:507–517Google Scholar
  299. Weglicki WB, Luna Z, Nair PP (1969) Sex and tissue specific differences in concentrations of alpha-tocopherol in mature and senescent rats. Nature 221:185–186Google Scholar
  300. Weiss B (2002) Sexually dimorphic nonreproductive behaviors as indicators of endocrine disruption. Environ Health Perspect 110(Suppl 3):387–391Google Scholar
  301. Werling DM (2016) The role of sex-differential biology in risk for autism spectrum disorder. Biol Sex Differ 7:58.  https://doi.org/10.1186/s13293-016-0112-8 Google Scholar
  302. West RK, Maynard ME, Leasure JL (2018) Binge ethanol effects on prefrontal cortex neurons, spatial working memory and task-induced neuronal activation in male and female rats. Physiol Behav 188:79–85.  https://doi.org/10.1016/j.physbeh.2018.01.027 Google Scholar
  303. Wexler NS et al (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci U S A 101:3498–3503.  https://doi.org/10.1073/pnas.0308679101 Google Scholar
  304. Wickens MM, Bangasser DA, Briand LA (2018) Sex differences in psychiatric disease: a focus on the glutamate system. Front Mol Neurosci 11:197.  https://doi.org/10.3389/fnmol.2018.00197 Google Scholar
  305. Wiener C et al (2014) Gender-based differences in oxidative stress parameters do not underlie the differences in mood disorders susceptibility between sexes. Eur Psychiatry 29:58–63.  https://doi.org/10.1016/j.eurpsy.2013.05.006 Google Scholar
  306. Will TR et al (2017) Problems and progress regarding sex bias and omission in neuroscience research. eNeuro:4.  https://doi.org/10.1523/eneuro.0278-17.2017
  307. Wise LM, Sadowski RN, Kim T, Willing J, Juraska JM (2016) Long-term effects of adolescent exposure to bisphenol A on neuron and glia number in the rat prefrontal cortex: differences between the sexes and cell type. Neurotoxicology 53:186–192.  https://doi.org/10.1016/j.neuro.2016.01.011 Google Scholar
  308. Wojnar M, Wasilewski D, Matsumoto H, Cedro A (1997) Differences in the course of alcohol withdrawal in women and men: a Polish sample. Alcohol Clin Exp Res 21:1351–1355Google Scholar
  309. Wood SJ, Yucel M, Pantelis C, Berk M (2009) Neurobiology of schizophrenia spectrum disorders: the role of oxidative stress. Ann Acad Med Singap 38:396–396Google Scholar
  310. Wu J, Williams D, Walter GA, Thompson WE, Sidell N (2014) Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells. Exp Cell Res 328:351–360.  https://doi.org/10.1016/j.yexcr.2014.08.030 Google Scholar
  311. Xiong XY, Wang J, Qian ZM, Yang QW (2014) Iron and intracerebral hemorrhage: from mechanism to translation. Transl Stroke Res 5:429–441.  https://doi.org/10.1007/s12975-013-0317-7 Google Scholar
  312. Xu X, Ha SU, Basnet R (2016) A review of epidemiological research on adverse neurological effects of exposure to ambient air pollution. Front Public Health 4:157.  https://doi.org/10.3389/fpubh.2016.00157 Google Scholar
  313. Yan W et al (2017) Testosterone upregulates the expression of mitochondrial ND1 and ND4 and alleviates the oxidative damage to the nigrostriatal dopaminergic system in orchiectomized rats. Oxidative Med Cell Longev 2017:1202459.  https://doi.org/10.1155/2017/1202459 Google Scholar
  314. Yan Y, Dominguez S, Fisher DW, Dong H (2018) Sex differences in chronic stress responses and Alzheimer’s disease. Neurobiol Stress 8:120–126.  https://doi.org/10.1016/j.ynstr.2018.03.002 Google Scholar
  315. Yang X et al (2006) Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 16:995–1004.  https://doi.org/10.1101/gr.5217506 Google Scholar
  316. Yao JK, Leonard S, Reddy R (2006) Altered glutathione redox state in schizophrenia. Dis Markers 22:83–93Google Scholar
  317. Yeh JY, Ou BR, Gu QP, Whanger PD (1998) Influence of gender on selenoprotein W, glutathione peroxidase and selenium in tissues of rats. Comp Biochem Physiol B Biochem Mol Biol 119:151–155Google Scholar
  318. Yonehara K, Suzuki M, Yamanouchi K, Nishihara M (2003) Expression analyses of sex steroid-regulated genes in neonatal rat hypothalamus. J Reprod Dev 49:547–552Google Scholar
  319. You JM, Yun SJ, Nam KN, Kang C, Won R, Lee EH (2009) Expression analyses of sex steroid-regulated genes in neonatal rat hypothalamus. Can J Physiol Pharmacol 87:440–447.  https://doi.org/10.1139/y09-027 Google Scholar
  320. Zechner U, Wilda M, Kehrer-Sawatzki H, Vogel W, Fundele R, Hameister H (2001) A high density of X-linked genes for general cognitive ability: a run-away process shaping human evolution? Trends Genet 17:697–701Google Scholar
  321. Zhang XY et al (2009) Superoxide dismutase and cytokines in chronic patients with schizophrenia: association with psychopathology and response to antipsychotics. Psychopharmacology 204:177–184.  https://doi.org/10.1007/s00213-008-1447-6 Google Scholar
  322. Zhang GL, Wang W, Kang YX, Xue Y, Yang H, Zhou CM, Shi GM (2013) Chronic testosterone propionate supplement could activated the Nrf2-ARE pathway in the brain and ameliorated the behaviors of aged rats. Behav Brain Res 252:388–395.  https://doi.org/10.1016/j.bbr.2013.05.063 Google Scholar
  323. Zhang C, Kuo CC, Moghadam SH, Monte L, Rice KC, Rissman RA (2015) Corticotropin-releasing factor Receptor-1 antagonism reduces oxidative damage in an Alzheimer’s disease transgenic mouse model. J Alzheimers Dis 45:639–650.  https://doi.org/10.3233/jad-141722 Google Scholar
  324. Zhang G et al (2016) Enhancement of dopaminergic activity and region-specific activation of Nrf2-ARE pathway by intranasal supplements of testosterone propionate in aged male rats. Horm Behav 80:103–116.  https://doi.org/10.1016/j.yhbeh.2016.02.001 Google Scholar
  325. Zhang M, Wu J, Ding H, Wu W, Xiao G (2017) Progesterone provides the pleiotropic neuroprotective effect on traumatic brain injury through the Nrf2/ARE signaling pathway. Neurocrit Care 26:292–300.  https://doi.org/10.1007/s12028-016-0342-y Google Scholar
  326. Zhu Y, Carvey PM, Ling Z (2006) Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res 1090:35–44.  https://doi.org/10.1016/j.brainres.2006.03.063 Google Scholar
  327. Zielonka D et al (2013) The influence of gender on phenotype and disease progression in patients with ‘ disease. Parkinsonism Relat Disord 19:192–197.  https://doi.org/10.1016/j.parkreldis.2012.09.012 Google Scholar
  328. Zieminska E, Stafiej A, Toczylowska B, Lazarewicz JW (2012) Synergistic neurotoxicity of oxygen-glucose deprivation and tetrabromobisphenol A in vitro: role of oxidative stress. Pharmacol Rep 64:1166–1178Google Scholar
  329. Zieminska E, Lenart J, Diamandakis D, Lazarewicz JW (2017) The role of Ca2+ imbalance in the induction of acute oxidative stress and cytotoxicity in cultured rat cerebellar granule cells challenged with tetrabromobisphenol a. Neurochem Res 42:777–787.  https://doi.org/10.1007/s11064-016-2075-x Google Scholar
  330. Zoroglu SS, Armutcu F, Ozen S, Gurel A, Sivasli E, Yetkin O, Meram I (2004) Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 254:143–147.  https://doi.org/10.1007/s00406-004-0456-7 Google Scholar
  331. Zou Y et al (2017) Prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERbeta suppression in the amygdala. Mol Autism 8:46.  https://doi.org/10.1186/s13229-017-0159-3 Google Scholar
  332. Zuo W, Zhang W, Chen NH (2013) Sexual dimorphism in cerebral ischemia injury. Eur J Pharmacol 711:73–79.  https://doi.org/10.1016/j.ejphar.2013.04.024 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular PharmacologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Instituto de Biomedicina de SevillaHospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain
  3. 3.Yaroslavl State UniversityYaroslavlRussia
  4. 4.Peoples’ Friendship University of Russia (RUDN University)MoscowRussia
  5. 5.All-Russian Research Institute of Medicinal and Aromatic Plants (VILAR)MoscowRussia
  6. 6.Department of Forensic Sciences and Toxicology, School of MedicineUniversity of CreteHeraklionGreece

Personalised recommendations