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Journal of Molecular Neuroscience

, Volume 69, Issue 2, pp 298–311 | Cite as

Characterization of Motor and Non-Motor Behavioral Alterations in the Dj-1 (PARK7) Knockout Rat

  • Tara L. Kyser
  • Adam J. Dourson
  • Jennifer L. McGuire
  • Ann M. Hemmerle
  • Michael T. Williams
  • Kim B. SeroogyEmail author
Article

Abstract

Parkinson’s disease is a neurodegenerative disorder that encompasses a constellation of motor and non-motor symptoms. The etiology of the disease is still poorly understood because of complex interactions between environmental and genetic risk factors. Using animal models to assess these risk factors may lead to a better understanding of disease manifestation. In this study, we assessed the Dj-1 knockout (KO) genetic rat model in a battery of motor and non-motor behaviors. We tested the Dj-1 KO rat, as well as age-matched wild-type (WT) control rats, in several sensorimotor tests at 2, 4, 7, and 13 months of age. The Dj-1-deficient rats were found to rear and groom less, and to have a shorter stride length than their WT counterparts, but to take more forelimb and hindlimb steps. In non-motor behavioral tasks, performed at several different ages, we evaluated the following: olfactory function, anxiety-like behavior, short-term memory, anhedonia, and stress coping behavior. Non-motor testing was conducted as early as 4.5 months and as late as 17 months of age. We found that Dj-1 KO animals displayed deficits in short-term spatial memory as early as 4.5 months of age during place preference testing, as well as impaired coping strategies in the forced swim test, which are consistent with a parkinsonian-like phenotype. In some instances, effects of chronic stress were evaluated in the Dj-1-deficient rats, as an initial test of an environmental challenge combined with a genetic disposition for PD. Although some of the results were mixed with differential effects across several of the behaviors, the combination of the changes we observed indicates that the Dj-1 KO rat may be a promising model for the assessment of the prodromal stage of Parkinson’s disease, but further evaluation is necessary.

Keywords

Parkinson’s disease DJ-1 PARK7 Knockout rat Motor behavior Non-motor behavior 

Notes

Acknowledgments

We are grateful to Dr. Sheila Fleming for expert training in several of the behavioral tasks. This work was supported by the Kerman Family Fund, the Selma Schottenstein Harris Lab for Research in Parkinson’s, the Gardner Family Center for Parkinson’s Disease and Movement Disorders, and the Parkinson’s Disease Support Network - Ohio, Kentucky and Indiana. AMH was supported by National Institutes of Health grant T32 DK059803.

Compliance with Ethical Standards

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All protocols were approved by the University of Cincinnati Institutional Animal Care and Use Committee.

References

  1. Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P (2001) Risk of dementia in Parkinson's disease: a community-based, prospective study. Neurology 56:730–736CrossRefGoogle Scholar
  2. Aarsland D, Marsh L, Schrag A (2009) Neuropsychiatric symptoms in Parkinson's disease. Mov Disord 24:2175–2186CrossRefGoogle Scholar
  3. Agid Y, Graybiel AM, Ruberg M, Hirsch E, Blin J, Dubois B, Javoy-Agid F (1990) The efficacy of levodopa treatment declines in the course of Parkinson's disease: do nondopaminergic lesions play a role? Adv Neurol 53:83–100Google Scholar
  4. Alberts JR, Galef BG Jr (1971) Acute anosmia in the rat: a behavioral test of a peripherally-induced olfactory deficit. Physiol Behav 6:619–621CrossRefGoogle Scholar
  5. Andres-Mateos E, Perier C, Zhang L, Blanchard-Fillion B, Greco TM, Thomas B, Ko HS, Sasaki M, Ischiropoulos H, Przedborski S, Dawson TM, Dawson VL (2007) DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc Natl Acad Sci U S A 104:14807–14812CrossRefGoogle Scholar
  6. Archer J (1975) Rodent sex differences in emotional and related behavior. Behav Biol 14:451–479CrossRefGoogle Scholar
  7. Aviles-Olmos I, Limousin P, Lees A, Foltynie T (2013) Parkinson's disease, insulin resistance and novel agents of neuroprotection. Brain 136:374–384CrossRefGoogle Scholar
  8. Balestrino R, Martinez-Martin P (2017) Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson's disease. J Neurol Sci 373:173–178CrossRefGoogle Scholar
  9. Beeler JA, Cao ZF, Kheirbek MA, Zhuang X (2009) Loss of cocaine locomotor response in Pitx3-deficient mice lacking a nigrostriatal pathway. Neuropsychopharmacology 34:1149–1161CrossRefGoogle Scholar
  10. Blackinton J, Lakshminarasimhan M, Thomas KJ, Ahmad R, Greggio E, Raza AS, Cookson MR, Wilson MA (2009) Formation of a stabilized cysteine sulfinic acid is critical for the mitochondrial function of the parkinsonism protein DJ-1. J Biol Chem 284:6476–6485CrossRefGoogle Scholar
  11. Boesveldt S, Verbaan D, Knol DL, Visser M, van Rooden SM, van Hilten JJ, Berendse HW (2008) A comparative study of odor identification and odor discrimination deficits in Parkinson's disease. Mov Disord 23:1984–1990CrossRefGoogle Scholar
  12. Bogdanova OV, Kanekar S, D'Anci KE, Renshaw PF (2013) Factors influencing behavior in the forced swim test. Physiol Behav 118:227–239CrossRefGoogle Scholar
  13. Boger HA, Granholm AC, McGinty JF, Middaugh LD (2010) A dual-hit animal model for age-related parkinsonism. Prog Neurobiol 90:217–229CrossRefGoogle Scholar
  14. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259CrossRefGoogle Scholar
  15. Bonnet AM, Loria Y, Saint-Hilaire MH, Lhermitte F, Agid Y (1987) Does long-term aggravation of Parkinson's disease result from nondopaminergic lesions? Neurology 37:1539–1542CrossRefGoogle Scholar
  16. Braun AA, Skelton MR, Vorhees CV, Williams MT (2011) Comparison of the elevated plus and elevated zero mazes in treated and untreated male Sprague-Dawley rats: effects of anxiolytic and anxiogenic agents. Pharmacol Biochem Behav 97:406–415CrossRefGoogle Scholar
  17. Broeders M, Velseboer DC, de Bie R, Speelman JD, Muslimovic D, Post B, de Haan R, Schmand B (2013) Cognitive change in newly-diagnosed patients with Parkinson's disease: a 5-year follow-up study. J Int Neuropsychol Soc 19:695–708CrossRefGoogle Scholar
  18. Brønnick K, Alves G, Aarsland D, Tysnes OB, Larsen JP (2011) Verbal memory in drug-naive, newly diagnosed Parkinson's disease. The retrieval deficit hypothesis revisited Neuropsychology 25:114–124Google Scholar
  19. Brown JA, Emnett RJ, White CR, Yuede CM, Conyers SB, O'Malley KL, Wozniak DF, Gutmann DH (2010) Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice. Hum Mol Genet 19:4515–4528CrossRefGoogle Scholar
  20. Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D (2008) Dementia and survival in Parkinson disease: a 12-year population study. Neurology 70:1017–1022CrossRefGoogle Scholar
  21. Chandran JS, Lin X, Zapata A, Hoke A, Shimoji M, Moore SO, Galloway MP, Laird FM, Wong PC, Price DL, Bailey KR, Crawley JN, Shippenberg T, Cai H (2008) Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function. Neurobiol Dis 29:505–514CrossRefGoogle Scholar
  22. Chang JW, Wachtel SR, Young D, Kang UJ (1999) Biochemical and anatomical characterization of forepaw adjusting steps in rat models of Parkinson's disease: studies on medial forebrain bundle and striatal lesions. Neuroscience 88:617–628CrossRefGoogle Scholar
  23. Chaudhuri KR, Healy DG, Schapira AH, National Institute for Clinical Excellence (2006) Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 5:235–245CrossRefGoogle Scholar
  24. Chen L, Cagniard B, Mathews T, Jones S, Koh HC, Ding Y, Carvey PM, Ling Z, Kang UJ, Zhuang X (2005) Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J Biol Chem 280:21418–21426CrossRefGoogle Scholar
  25. Cookson MR (2012) Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways. Cold Spring Harb Perspect Med 2:a009415CrossRefGoogle Scholar
  26. Cronin-Golomb A, Braun AE (1997) Visuospatial dysfunction and problem solving in Parkinson's disease. Neuropsychology 11:44–52CrossRefGoogle Scholar
  27. Cummings JL (1992) Depression and Parkinson's disease: a review. Am J Psychiatry 149:443–454CrossRefGoogle Scholar
  28. Dave KD, De Silva S, Sheth NP, Ramboz S, Beck MJ, Quang C, Switzer RC 3rd, Ahmad SO, Sunkin SM, Walker D, Cui X, Fisher DA, McCoy AM, Gamber K, Ding X, Goldberg MS, Benkovic SA, Haupt M, Baptista MA, Fiske BK, Sherer TB, Frasier MA (2014) Phenotypic characterization of recessive gene knockout rat models of Parkinson’s disease. Neurobiol Dis 70:190–203CrossRefGoogle Scholar
  29. de Kloet ER, Molendijk ML (2016) Coping with the forced swim stressor: towards understanding an adaptive mechanism. Neural Plast 2016:6503162CrossRefGoogle Scholar
  30. Deng H, Wang P, Jankovic J (2018) The genetics of Parkinson disease. Ageing Res Rev 42:72-85Google Scholar
  31. Doty RL (2012) Olfactory dysfunction in Parkinson disease. Nat Rev Neurol 8:329–339CrossRefGoogle Scholar
  32. Doty RL, Deems DA, Stellar S (1988) Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 38:1237–1244CrossRefGoogle Scholar
  33. Dujardin K, Degreef JF, Rogelet P, Defebvre L, Destee A (1999) Impairment of the supervisory attentional system in early untreated patients with Parkinson's disease. J Neurol 246:783–788CrossRefGoogle Scholar
  34. Espay AJ, LeWitt PA, Kaufmann H (2014) Norepinephrine deficiency in Parkinson's disease: the case for noradrenergic enhancement. Mov Disord 29:1710–1719CrossRefGoogle Scholar
  35. Fahn S (1999) Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs later L-DOPA. Arch Neurol 56:529–535CrossRefGoogle Scholar
  36. Farrer MJ (2006) Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet 7:306–318CrossRefGoogle Scholar
  37. Fleming SM, Salcedo J, Fernagut PO, Rockenstein E, Masliah E, Levine MS, Chesselet MF (2004) Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. J Neurosci 24:9434–9440CrossRefGoogle Scholar
  38. Fleming SM, Tetreault NA, Mulligan CK, Hutson CB, Masliah E, Chesselet MF (2008) Olfactory deficits in mice overexpressing human wildtype alpha-synuclein. Eur J Neurosci 28:247–256CrossRefGoogle Scholar
  39. Fleming SM, Ekhator OR, Ghisays V (2013) Assessment of sensorimotor function in mouse models of Parkinson's disease. J Vis Exp (76).  https://doi.org/10.3791/50303
  40. Francardo V (2018) Modeling Parkinson's disease and treatment complications in rodents: potentials and pitfalls of the current options. Behav Brain Res 352:142–150CrossRefGoogle Scholar
  41. Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC, Klapstein GJ, Gajendiran M, Roth BL, Chesselet MF, Maidment NT, Levine MS, Shen J (2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278:43628–43635CrossRefGoogle Scholar
  42. Goldberg MS, Pisani A, Haburcak M, Vortherms TA, Kitada T, Costa C, Tong Y, Martella G, Tscherter A, Martins A, Bernardi G, Roth BL, Pothos EN, Calabresi P, Shen J (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45:489–496CrossRefGoogle Scholar
  43. Grimbergen YA, Langston JW, Roos RA, Bloem BR (2009) Postural instability in Parkinson's disease: the adrenergic hypothesis and the locus coeruleus. Expert Rev Neurother 9:279–290CrossRefGoogle Scholar
  44. Halliday G, Hely M, Reid W, Morris J (2008) The progression of pathology in longitudinally followed patients with Parkinson's disease. Acta Neuropathol 115:409–415CrossRefGoogle Scholar
  45. Hemmerle AM, Herman JP, Seroogy KB (2012) Stress, depression and Parkinson's disease. Exp Neurol 233:79–86CrossRefGoogle Scholar
  46. Hemmerle AM, Dickerson JW, Herman JP, Seroogy KB (2014) Stress exacerbates experimental Parkinson's disease. Mol Psychiatry 19:638–640CrossRefGoogle Scholar
  47. Hennis MR, Marvin MA, Taylor CM 2nd, Goldberg MS (2014) Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease. Neurobiol Dis 62:113–123CrossRefGoogle Scholar
  48. Herbert MK, Eeftens JM, Aerts MB, Esselink RA, Bloem BR, Kuiperij HB, Verbeek MM (2014) CSF levels of DJ-1 and tau distinguish MSA patients from PD patients and controls. Parkinsonism Relat Disord 20:112–115CrossRefGoogle Scholar
  49. Herman JP, Adams D, Prewitt C (1995) Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm. Neuroendocrinology 61:180–190CrossRefGoogle Scholar
  50. Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 133:713–726CrossRefGoogle Scholar
  51. Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A, You-Ten AJ, Kalia SK, Horne P, Westaway D, Lozano AM, Anisman H, Park DS, Mak TW (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102:5215–5220CrossRefGoogle Scholar
  52. Kitada T, Tong Y, Gautier CA, Shen J (2009) Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J Neurochem 111:696–702CrossRefGoogle Scholar
  53. Krebiehl G, Ruckerbauer S, Burbulla LF, Kieper N, Maurer B, Waak J, Wolburg H, Gizatullina Z, Gellerich FN, Woitalla D, Riess O, Kahle PJ, Proikas-Cezanne T, Kruger R (2010) Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1. PLoS One 5:e9367CrossRefGoogle Scholar
  54. Lewis SJ, Cools R, Robbins TW, Dove A, Barker RA, Owen AM (2003) Using executive heterogeneity to explore the nature of working memory deficits in Parkinson's disease. Neuropsychologia 41:645–654CrossRefGoogle Scholar
  55. Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185Google Scholar
  56. Manning-Bog AB, Caudle WM, Perez XA, Reaney SH, Paletzki R, Isla MZ, Chou VP, McCormack AL, Miller GW, Langston JW, Gerfen CR, Dimonte DA (2007) Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter. Neurobiol Dis 27:141–150CrossRefGoogle Scholar
  57. Masters JM, Noyce AJ, Warner TT, Giovannoni G, Proctor GB (2015) Elevated salivary protein in Parkinson's disease and salivary DJ-1 as a potential marker of disease severity. Parkinsonism Relat Disord 21:1251–1255CrossRefGoogle Scholar
  58. McDonald WM, Richard IH, DeLong MR (2003) Prevalence, etiology, and treatment of depression in Parkinson's disease. Biol Psychiatry 54:363–375CrossRefGoogle Scholar
  59. Mesholam RI, Moberg PJ, Mahr RN, Doty RL (1998) Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases. Arch Neurol 55:84–90CrossRefGoogle Scholar
  60. Molendijk ML, de Kloet ER (2015) Immobility in the forced swim test is adaptive and does not reflect depression. Psychoneuroendocrinology 62:389–391CrossRefGoogle Scholar
  61. Nathan BP, Yost J, Litherland MT, Struble RG, Switzer PV (2004) Olfactory function in apoE knockout mice. Behav Brain Res 150:1–7CrossRefGoogle Scholar
  62. Olsson M, Nikkhah G, Bentlage C, Björklund A (1995) Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J Neurosci 15:3863–3875CrossRefGoogle Scholar
  63. Overstreet DH (2002) Behavioral characteristics of rat lines selected for differential hypothermic responses to cholinergic or serotonergic agonists. Behav Genet 32:335–348CrossRefGoogle Scholar
  64. Pedersen KF, Larsen JP, Tysnes OB, Alves G (2017) Natural course of mild cognitive impairment in Parkinson disease: a 5-year population-based study. Neurology 88:767–774CrossRefGoogle Scholar
  65. Peng J, Oo ML, Andersen JK (2010) Synergistic effects of environmental risk factors and gene mutations in Parkinson's disease accelerate age-related neurodegeneration. J Neurochem 115:1363–1373CrossRefGoogle Scholar
  66. Pham TT, Giesert F, Rothig A, Floss T, Kallnik M, Weindl K, Holter SM, Ahting U, Prokisch H, Becker L, Klopstock T, Hrabe de Angelis M, Beyer K, Gorner K, Kahle PJ, Vogt Weisenhorn DM, Wurst W (2010) DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area and exhibit non-motoric behavioural impairments. Genes Brain Behav 9:305–317CrossRefGoogle Scholar
  67. Ponsen MM, Stoffers D, Booij J, van Eck-Smit BL, Wolters EC, Berendse HW (2004) Idiopathic hyposmia as a preclinical sign of Parkinson's disease. Ann Neurol 56:173–181CrossRefGoogle Scholar
  68. Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732CrossRefGoogle Scholar
  69. Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391CrossRefGoogle Scholar
  70. Rampersaud N, Harkavyi A, Giordano G, Lever R, Whitton J, Whitton PS (2012) Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson's disease with combined noradrenergic and serotonergic lesions. Neuropeptides 46:183–193CrossRefGoogle Scholar
  71. Rascol O (2000) The pharmacological therapeutic management of levodopa-induced dyskinesias in patients with Parkinson's disease. J Neurol 247(Suppl 2):II51–II57Google Scholar
  72. Richard IH (2005) Anxiety disorders in Parkinson's disease. Adv Neurol 96:42–55Google Scholar
  73. Riedel O, Klotsche J, Spottke A, Deuschl G, Forstl H, Henn F, Heuser I, Oertel W, Reichmann H, Riederer P, Trenkwalder C, Dodel R, Wittchen HU (2010) Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson's disease. J Neurol 257:1073–1082CrossRefGoogle Scholar
  74. Rommelfanger KS, Edwards GL, Freeman KG, Liles LC, Miller GW, Weinshenker D (2007) Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proc Natl Acad Sci U S A 104:13804–13809CrossRefGoogle Scholar
  75. Rousseaux MW, Marcogliese PC, Qu D, Hewitt SJ, Seang S, Kim RH, Slack RS, Schlossmacher MG, Lagace DC, Mak TW, Park DS (2012) Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proc Natl Acad Sci U S A 109:15918–15923CrossRefGoogle Scholar
  76. Sandyk R (1993) The relationship between diabetes mellitus and Parkinson's disease. Int J Neurosci 69:125–130CrossRefGoogle Scholar
  77. Schallert T, Tillerson JL (2000) Intervention strategies for degeneration of DA neurons in parkinsonism: optimizing behavioral assessment of outcome. In: Emerich D, Dean R III, Sandberg P (eds) Central nervous system diseases. Humana, Totowa, p 131CrossRefGoogle Scholar
  78. Schallert T, Whishaw IQ, Ramirez VD, Teitelbaum P (1978) Compulsive, abnormal walking caused by anticholinergics in akinetic, 6-hydroxydopamine-treated rats. Science 199:1461–1463CrossRefGoogle Scholar
  79. Schallert T, De Ryck M, Whishaw IQ, Ramirez VD, Teitelbaum P (1979) Excessive bracing reactions and their control by atropine and L-DOPA in an animal analog of Parkinsonism. Exp Neurol 64:33–43CrossRefGoogle Scholar
  80. Schallert T, Upchurch M, Lobaugh N, Farrar SB, Spirduso WW, Gilliam P, Vaughn D, Wilcox RE (1982) Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage. Pharmacol Biochem Behav 16:455–462CrossRefGoogle Scholar
  81. Schallert T, Upchurch M, Wilcox RE, Vaughn DM (1983) Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriatum. Pharmacol Biochem Behav 18:753–759CrossRefGoogle Scholar
  82. Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST (2000) CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 39:777–787CrossRefGoogle Scholar
  83. Schapira AH (2009) Neurobiology and treatment of Parkinson's disease. Trends Pharmacol Sci 30:41–47CrossRefGoogle Scholar
  84. Schrag A, Taddei RN (2017) Depression and anxiety in Parkinson's disease. Int Rev Neurobiol 133:623–655CrossRefGoogle Scholar
  85. Sherer TB, Betarbet R, Greenamyre JT (2002) Environment, mitochondria, and Parkinson's disease. Neuroscientist 8:192–197Google Scholar
  86. Smith AD, Castro SL, Zigmond MJ (2002) Stress-induced Parkinson's disease: a working hypothesis. Physiol Behav 77:527–531CrossRefGoogle Scholar
  87. Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5:213–218CrossRefGoogle Scholar
  88. Tröster AI (2008) Neuropsychological characteristics of dementia with Lewy bodies and Parkinson’s disease with dementia: differentiation, early detection, and implications for “mild cognitive impairment” and biomarkers. Neuropsychol Rev 18:103–119Google Scholar
  89. Vingill S, Connor-Robson N, Wade-Martins R (2018) Are rodent models of Parkinson's disease behaving as they should? Behav Brain Res 352:133–141CrossRefGoogle Scholar
  90. Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83:482–504CrossRefGoogle Scholar
  91. Willner P (2005) Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52:90–110CrossRefGoogle Scholar
  92. Wulsin AC, Herman JP, Solomon MB (2010) Mifepristone decreases depression-like behavior and modulates neuroendocrine and central hypothalamic-pituitary-adrenocortical axis responsiveness to stress. Psychoneuroendocrinology 35:1100–1112CrossRefGoogle Scholar
  93. Yamaguchi H, Shen J (2007) Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice. Mol Neurodegener 2:10CrossRefGoogle Scholar
  94. Yang KM, Blue KV, Mulholland HM, Kurup MP, Kelm-Nelson CA, Ciucci MR (2018) Characterization of oromotor and limb motor dysfunction in the DJ1 −/− model of Parkinson disease. Behav Brain Res 339:47–56CrossRefGoogle Scholar
  95. Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL (2006) The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. J Mol Biol 356:1036–1048CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Cincinnati College of MedicineCincinnatiUSA
  2. 2.Neuroscience Graduate ProgramUniversity of CincinnatiCincinnatiUSA
  3. 3.Department of AnesthesiaCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  4. 4.Department of NeurosurgeryUniversity of Cincinnati College of MedicineCincinnatiUSA
  5. 5.Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiUSA
  6. 6.Division of NeurologyCincinnati Children’s Research FoundationCincinnatiUSA
  7. 7.The Selma Schottenstein Harris Laboratory for Research in Parkinson’s, Gardner Family Center for Parkinson’s Disease and Movement Disorders, Department of NeurologyUniversity of Cincinnati College of MedicineCincinnatiUSA

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