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Taurine 11 pp 821-846 | Cite as

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

  • Lorenz S. NeuwirthEmail author
  • Youngjoo Kim
  • Eddy D. Barrerra
  • Cyrus Jo
  • Jean-Martin Chrisphonte
  • Nimra Hameed
  • Samantha Rubi
  • Teddy F. DaciusJr.
  • Jourvonn C. Skeen
  • Jalen R. Bonitto
  • Eric Khairi
  • Asma Iqbal
  • Isra Ahmed
  • Sidrah Masood
  • Bettina Tranquilee
  • Veni Thiruverkadu
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1155)

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.

Keywords

Attention-set-shift test Lead poisoning Developmental neurotoxicity Taurine Frontoexecutive functions Psychopharmacotherapy 

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

Notes

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 Neuwirth™ ASST apparatus. Otherwise, the authors declare no other conflicts of interest.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Lorenz S. Neuwirth
    • 1
    • 2
    Email author
  • Youngjoo Kim
    • 3
    • 4
  • Eddy D. Barrerra
    • 1
    • 2
  • Cyrus Jo
    • 2
    • 5
  • Jean-Martin Chrisphonte
    • 2
    • 4
  • Nimra Hameed
    • 2
    • 5
  • Samantha Rubi
    • 2
    • 5
  • Teddy F. DaciusJr.
    • 1
    • 2
  • Jourvonn C. Skeen
    • 2
    • 5
  • Jalen R. Bonitto
    • 2
    • 5
  • Eric Khairi
    • 2
    • 5
  • Asma Iqbal
    • 1
    • 2
  • Isra Ahmed
    • 1
    • 2
  • Sidrah Masood
    • 1
    • 2
  • Bettina Tranquilee
    • 2
    • 5
  • Veni Thiruverkadu
    • 2
    • 5
  1. 1.Department of PsychologySUNY Old WestburyOld WestburyUSA
  2. 2.SUNY Neuroscience Research InstituteSUNY Old WestburyOld WestburyUSA
  3. 3.Department of Chemistry & PhysicsSUNY Old WestburyOld WestburyUSA
  4. 4.iCARE InstituteSUNY Old WestburyOld WestburyUSA
  5. 5.Department of BiologySUNY Old WestburyOld WestburyUSA

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