Abstract
Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognitive and behavioral systems. The present study evaluated the effects of developmental Pb2+-exposure (150 ppm lead acetate in the drinking water) in Long Evans Hooded rats through the Attention Set-Shift Test (ASST) between postnatal days (PND) 60–90. Treatment groups were comprised of Control (0 ppm), Perinatal (150 ppm), and Perinatal+Taurine (150 ppm + 0.05% Taurine in the drinking water) rats (N = 36; n = 6 per treatment group for each sex). Frontoexecutive functions were evaluated based on trials-to-criterion (TTC) and errors-to-criterion (ETC) measures for simple and complex discriminations (SD & CD), intradimensional and extradimensional shifts (ID & ED), as well as reversals (Rev) of the CD, I-, and ED stages, respectively. Post-testing, the prelimbic (PrL), infralimbic (IL), orbital ventral frontal (OV), orbital ventro-lateral (OVL), and hippocampal (HP) brain regions were extracted and processed through Liquid Chromatography/Mass Spectrophotometry (LC/MS) for determining the GABA and Taurine ratios relative to Glutamate, Dopamine, Norepinephrine, Epinephrine, and Serotonin. The ASST data revealed that Perinatal rats are negatively impacted by developmental Pb2+-exposures evidenced by increased TTC and ETC to learn the SD, ID, and ID-Rev with unique sex-based differences in frontoexecutive dysfunctions. Moreover, Perinatal+Taurine co-treated rats exhibited a recovery of the frontoexecutive dysfunctions observed in Perinatal rats to levels equivalent to Control rats across both sexes. The LC/MS data revealed altered brain sub-region specific patterns across the PrL, IL, OV, OVL, and HP in response to developmental Pb2+-exposure that produced an altered neurochemical signaling profile in a sex-dependent manner, which may underlie the observed frontoexecutive dysfunctions, cognitive inflexibility, and associated motivation deficits. When taurine co-treatment was administered concurrently for the duration of developmental Pb2+-exposure, the observed frontoexecutive dysfunctions were significantly reduced in both ASST task performance and neurochemical ratios that were comparable to Control levels for both sexes. Altogether, the data suggest that taurine co-treatment may facilitate neuroprotection, mitigate neurotransmitter excitability balancing, and perhaps ameliorate against neurotoxicant exposures in early development as a potential psychopharmacotherapy.
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Abbreviations
- AD/HD:
-
attention deficit/hyper activity disorder
- ASST:
-
attention set-shift test
- ASV:
-
anodic stripping voltammetry
- BLL:
-
blood lead level
- CD:
-
complex discrimination
- CD-ReAcq:
-
compound discrimination re-acquisition
- CD-Rev:
-
complex discrimination reversal
- ED:
-
extradimensional shift
- ED-Rev:
-
extradimensional shift reversal
- EDTA:
-
ethylenediaminetetracetic acid
- ETC:
-
errors to criterion
- HP:
-
hippocampal area
- HPLC:
-
high performance liquid chromatography
- ID:
-
intradimensional shift
- ID-ReAcq:
-
intra-dimensional shift re-acquisition
- ID-Rev:
-
intradimensional reversal
- IL:
-
infralimbic area
- LC/MS:
-
liquid chromatography/mass spectrophotometry
- OV:
-
orbital ventral frontal area
- OVL:
-
orbital ventral lateral area
- Pb2+:
-
lead
- PND:
-
postnatal day
- PrL:
-
prelimbic area
- SD:
-
simple discrimination
- Tau:
-
taurine
- TTC:
-
trials-to-criterion
- WCST:
-
Wisconsin Card Sorting Task
References
Arnsten AFT (2009) Stress signaling pathways that impair prefrontal cortex structure and function. Nat Rev 10:410–422
Aron AR, Poldrack RA (2005) The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1285–1292
Ben-Ari Y (2002) Excitatory actions of GABA during development: the nature or the nurture. Nat Rev Neurosci (9):728–739
Ben-Ari Y, Khalilov I, Kahle KT, Cherubini E (2012) The GABA excitatory/inhibitory shift in brain maturation and neurological disorders. Neuroscientist:1–20
Birrell, J.M. & Brown, V.J. (2000). Medial frontal cortex mediates perceptual attentional set shifting in the rat, 20(11): 4320–4324
Bizon JL, Foster TC, Alexander GE, Glisky EL (2012) Characterizing cognitive aging of working memory and executive function in animal models. Front Aging Neurosci 4(19):1–14
Canfield RL, Kreher DA, Cornwell C, Henderson CR Jr (2003) Low-level lead exposure, executive functioning, and early childhood. Clin Neuropsychol 9(1):35–53
Canfield RL, Gendle MH, Cory-Slechta DA (2004) Impaired neuropsychological functioning in lead-exposed children. Dev Neuropsychol 26(1):513–540
Canfield RL, Jusko TA, Kordas K (2005) Environmental lead exposure and children’s cognitive function. Riv Ital Pediat 31(6):293–300
Chan CY, Sun HS, Shah SM, Argovic MS, Friedman E, Banerjee SP (2014) Modes of direct modulation by taurine of the glutamate NMDA receptor in rat cortex. Eur J Pharmacol 728:167–175
Chudasama Y, Robbins TW (2006) Functions of frontostriatal systems in cognition: comparative neuropsychopharmacological studies in rats, monkeys and humans. Biol Psychol 73:19–38
Cory-Slechta DA (1995) Relationships between lead-induced learning impairments and changes in dopaminergic, cholinergic, and glutaminergic neurotransmitters system functions. Anna Rev Pharmacol Toxicol 35:391–415
Cory-Slechta DA, O’Mara DJ, Brockel BJ (1998) Nucleus accumbens dopaminergic medication of fixed interval schedule-controlled behavior and its modulation by low-level lead exposure. J Pharmacol Exp Therapeut 286(2):794–8055
Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784
El Idrissi A, Boukarrou L, Heany W, Malliaros G, Sangdee C, Neuwirth LS (2009) Effects of taurine on anxiety-like and locomotor behavior of mice. In: Azuma J, Schaffer SW, Takashi I (eds) Taurine 7: taurine for the future healthcare, vol 643. Springer Press, New York, pp 207–215
El Idrissi A, Iskra BS, Neuwirth LS (2011) Neurobehavioral effects of taurine in Fragile X syndrome. In: El Idrissi A, L’Amoreaux WJ (eds) Taurine 8: taurine in health and disease, vol 644. Springer Press, New York, pp 306–345
El-Ansary AK, Bacha AB, Ayahdi LYA (2011) Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudia Arabia. Clin Biochem 44(13):1116–1120
Gilmartin MR, Balderston NL, Helmstetter FJ (2014) Prefrontal cortical regulation of fear learning. Trends Neurosci 37(8):455–464
Govoni S, Memo M, Spano PF, Trabucchi M (1979) Chronic lead treatment differentially affects dopamine synthesis in various rat brain areas. Toxicology 12(3):343–349
Jason KM, Kellogg CK (1981) Neonatal lead exposure: effects on development of behavior and striatal dopamine neurons. Pharmacol Biochem Behv 15(4):641–649
Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS (2004) Neuropsychological assessment, 4th edn. Oxford University Press, New York
Lidsky TI, Schneider JS (2003) Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5–19
Lidsky TI, Schneider JS (2005) Autism and autistic symptoms associated with childhood lead poisoning. J Appl Res 5(1):80–87
Lidsky TI, Schneider JS (2006) Adverse effects of childhood lead poisoning: the clinical neuropsychological perspective. Environ Res 100:284–293
Lucchi L, Memo M, Airaghi ML, Spano PF, Trabucchi M (1980) Chronic lead treatment induces in rat a specific and differential effect on dopamine receptors in different brain areas. Brain Res 213(2):397–404
Milner B (1963) Effects of different brain lesions on card sorting: the role of the frontal lobes. Arch Neurol 9:90–100
National Institutes of Health (2017). Guidelines for diet control in laboratory animals. Animal Research Advisory Committee Guidelines. Retrieved February 11, 2018 https://oacu.oir.nih.gov/animal-research-advisory-committee-guidelines
Neuwirth LS (2014) The characterization of Pb2+ toxicity in rat neural development: An assessment of Pb2+ effects on the GABA shift in neural networks and implications for learning and memory disruption. UMI Proquest dissertations & theses 3612469. DAI/B 75-06(E), April 2014
Neuwirth LS (2018) Resurgent lead poisoning and renewed public attention towards environmental social justice issues: a review of current efforts and call to revitalize primary and secondary lead poisoning prevention for pregnant women, lactating mothers, and children within the U.S. Intl J Occupat Environ Health:1–15. https://doi.org/10.1080/10773525.2018/1507291
Neuwirth LS, Volpe NP, El Idrissi A (2013) Taurine effects on emotional learning and memory in aged mice: neurochemical alterations and differentiation in auditory cued fear and context conditioning. In: El Idrissi A, L’Amoreaux WJ (eds) Taurine 8: the nervous system, immune system, diabetes, and the cardiovascular system, Advances in experimental medicine and biology, vol 775. Springer Press, New York, pp 195–214
Neuwirth LS, Volpe NP, Ng S, Marsillo A, Corwin C, Madan N, Ferraro AM, El Idrissi A (2015) Taurine recovers mice emotional learning and memory disruptions associated with Fragile X Syndrome in context fear and auditory cued-conditioning. In Marcinkiewicz J, Schaffer SW (eds) Taurine 9, vol 803. Springer Press, New York, pp 425–438
Neuwirth LS, Volpe NP, Corwin C, Ng S, Madan N, Ferraro AM, Furman Y, El Idrissi A (2017) Taurine recovery of learning deficits induced by developmental Pb2+ exposure. In: Lee DH, Shaffer S, Park E, Kim HW (eds) Taurine 10: taurine and brain health, vol 975. Springer Press, New York, pp 39–55
Neuwirth LS, Phillips G, El Idrissi A (2018) Perinatal Pb2+ exposure alters the expression of genes related to the neurodevelopmental GABA-shift in postnatal rats. J Biomed Sci 25(45):1–11
Neuwirth LS, Masood S, Anderson DW, Schneider JS (2019a) The attention set-shifting test is sensitive for revealing sex-based impairments in executive functions following developmental lead exposure in rats. Behav Brain Res 366:126–134. https://doi.org/10.1016/j.bbr.2019.03.022
Neuwirth LS, Emenike BU, Barrera ED, Hameed N, Rubi S, Dacius Jr. TF, Skeen JC, Bonitto JR, Khairi E, Iqbal A, Ahmed I, Jose TJ, Lynch K, Khan M, Alvira A, Mathew N, Kaur S, Masood S, Tranquille, Thiruverkadu V (2019b) Chapter 69: Assessing the anxiolytic properties of taurine-derived compounds in rats following developmental lead exposure: a neurodevelopmental and behavioral pharmacological pilot study. Taurine 11: a healthful molecule (in press)
Rossouw J, Offermeier J, van Rooyen JM (1987) Apparent central neurotransmitter receptor changes induced by low-level exposure during different developmental phases in the rat. Toxicol Appl Pharmacol 91(1):132–139
Roy A, Bellinger D, Hu H, Schwartz J, Ettinger AS, Wright RO, Bouchard M, Palaniappan K, Balakrishnan K (2009) Lead exposure and behavior among young children in Chennai, India. Environ Health Perspect 117(10):1607–1611
Santora A, Neuwirth LS, L’Amoreaux WJ, El Idrissi A (2013) The effects of chronic taurine supplementation on motor learning. In: El Idrissi A, L’Amoreaux WJ (eds) Taurine 8: physiological roles and mechanisms of action, vol 775. Springer Press, New York, pp 177–185. https://doi.org/10.1007/978-1-4614-6130-2_15
Strużyñska L, Sulkowski G (2004) Relationships between glutamine, glutamate, and GABA in nerve endings under Pb-toxicity conditions. J Inorg Biochem 98(6):951–958
Tait DS, Bowman EM, Neuwirth LS, Brown VJ (2018) Assessment of Intradimensional/Extradimensional attentional set-shifting in rats. Neurosci Biobehav Rev 89:72–84
Acknowledgements
This study was supported by a SUNY Old Westbury Faculty Development grant awarded to L.S.N & Y.J.K. We would like to thank the Co-Directors of the SUNY Old Westbury Collegiate-Science Technology Entry Program (C-STEP) Dr. Patrick Cadet and Mrs. Monique Clark for supporting underrepresented minority (URM) research students. The following URM students were supported by the C-STEP program: E.D.B, N.H., S.R., T.F.D. Jr., J.S., J.R.B, E.K., A.I., I.A. & B.T. Lastly, we would like to thank the Biology, Chemistry & Physics Department, and the SUNY-Neuroscience Research Institute for sharing resources and space allocations to conduct this study.
Conflicts of Interest
LSN discloses a public domain trademark used under common law as the Neuwirthâ„¢ ASST apparatus. Otherwise, the authors declare no other conflicts of interest.
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Neuwirth, L.S. et al. (2019). Early Neurodevelopmental Exposure to Low Lead Levels Induces Fronto-executive Dysfunctions That Are Recovered by Taurine Co-treatment in the Rat Attention Set-Shift Test: Implications for Taurine as a Psychopharmacotherapy Against Neurotoxicants. In: Hu, J., Piao, F., Schaffer, S., El Idrissi, A., Wu, JY. (eds) Taurine 11. Advances in Experimental Medicine and Biology, vol 1155. Springer, Singapore. https://doi.org/10.1007/978-981-13-8023-5_70
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