An avian model for ascertaining the mechanisms of organophosphate neuroteratogenicity and its therapy with mesenchymal stem cell transplantation.

Adi Pinkas, Gadi Turgeman, Shay Tayeb, Joseph Yanai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction: A fast and simple model which uses animals lower on the evolutionary scale is beneficial for progress in neuroteratological research. Here, we established this novel model and applied it in the study of the detrimental effects of pre-hatch exposure to chlorpyrifos on neurogenesis and several neurotransmitter systems in the chick and their reversal, using mesenchymal stem cell (MSC) transplantation. Methods: Chicken eggs were injected with the organophosphate chlorpyrifos, 10. mg/kg eggs - a dose below the threshold for dysmorphology - on incubation days (ID) 0 and 5 and subsequently the embryos were subjected to intravenous transplantation of MSC on ID 13. Results: After hatching (day 1) the expression of the neurogenesis-related genes DCX (also confirmed by immunohistochemistry), BDNF, MAP 2, FGF 2, SOX 2 and VEGF in the lateral striatum area was decreased in the exposed group (p. <0.005). Among the studied neurotransmitter systems (serotonergic, dopaminergic and cholinergic), increased gene expression was demonstrated for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) with a corresponding decrease in serotonin receptor 1A (5HTR1A) (p. <0.05); no changes in gene expression of choline transporter, PKC beta and D2 were found following chlorpyrifos exposure. Conclusion: Transplantation of MSC reversed all the neurogenic and serotonergic alterations (p. <0.01). The study of chick embryo exposure to insults with subsequent MSC therapy provides a fast and simple model for elucidating the mechanisms of both the neuroteratogenicity and the therapy, steps that are critical for progress toward therapeutic applications.

Original languageEnglish (US)
Pages (from-to)73-81
Number of pages9
JournalNeurotoxicology and Teratology
Volume50
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Fingerprint

Mesenchymal Stem Cell Transplantation
Chlorpyrifos
Organophosphates
Stem cells
Neurogenesis
Eggs
Neurotransmitter Agents
Gene expression
Protein Kinase C beta
Tryptophan Hydroxylase
Gene Expression
Receptor, Serotonin, 5-HT1A
Brain-Derived Neurotrophic Factor
Tyrosine 3-Monooxygenase
Fibroblast Growth Factor 2
Chick Embryo
Cell- and Tissue-Based Therapy
Hatches
Mesenchymal Stromal Cells
Cholinergic Agents

Keywords

  • Adult neurogenesis
  • Chick model
  • Chlorpyrifos
  • Gene expression
  • Mesenchymal stem cell therapy
  • Neurotransmitter systems
  • Pre-hatch exposure

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

An avian model for ascertaining the mechanisms of organophosphate neuroteratogenicity and its therapy with mesenchymal stem cell transplantation. / Pinkas, Adi; Turgeman, Gadi; Tayeb, Shay; Yanai, Joseph.

In: Neurotoxicology and Teratology, Vol. 50, 01.07.2015, p. 73-81.

Research output: Contribution to journalArticle

@article{21664eb470744d159dd2da75b4a721e9,
title = "An avian model for ascertaining the mechanisms of organophosphate neuroteratogenicity and its therapy with mesenchymal stem cell transplantation.",
abstract = "Introduction: A fast and simple model which uses animals lower on the evolutionary scale is beneficial for progress in neuroteratological research. Here, we established this novel model and applied it in the study of the detrimental effects of pre-hatch exposure to chlorpyrifos on neurogenesis and several neurotransmitter systems in the chick and their reversal, using mesenchymal stem cell (MSC) transplantation. Methods: Chicken eggs were injected with the organophosphate chlorpyrifos, 10. mg/kg eggs - a dose below the threshold for dysmorphology - on incubation days (ID) 0 and 5 and subsequently the embryos were subjected to intravenous transplantation of MSC on ID 13. Results: After hatching (day 1) the expression of the neurogenesis-related genes DCX (also confirmed by immunohistochemistry), BDNF, MAP 2, FGF 2, SOX 2 and VEGF in the lateral striatum area was decreased in the exposed group (p. <0.005). Among the studied neurotransmitter systems (serotonergic, dopaminergic and cholinergic), increased gene expression was demonstrated for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) with a corresponding decrease in serotonin receptor 1A (5HTR1A) (p. <0.05); no changes in gene expression of choline transporter, PKC beta and D2 were found following chlorpyrifos exposure. Conclusion: Transplantation of MSC reversed all the neurogenic and serotonergic alterations (p. <0.01). The study of chick embryo exposure to insults with subsequent MSC therapy provides a fast and simple model for elucidating the mechanisms of both the neuroteratogenicity and the therapy, steps that are critical for progress toward therapeutic applications.",
keywords = "Adult neurogenesis, Chick model, Chlorpyrifos, Gene expression, Mesenchymal stem cell therapy, Neurotransmitter systems, Pre-hatch exposure",
author = "Adi Pinkas and Gadi Turgeman and Shay Tayeb and Joseph Yanai",
year = "2015",
month = "7",
day = "1",
doi = "10.1016/j.ntt.2015.06.004",
language = "English (US)",
volume = "50",
pages = "73--81",
journal = "Neurotoxicology and Teratology",
issn = "0892-0362",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - An avian model for ascertaining the mechanisms of organophosphate neuroteratogenicity and its therapy with mesenchymal stem cell transplantation.

AU - Pinkas, Adi

AU - Turgeman, Gadi

AU - Tayeb, Shay

AU - Yanai, Joseph

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Introduction: A fast and simple model which uses animals lower on the evolutionary scale is beneficial for progress in neuroteratological research. Here, we established this novel model and applied it in the study of the detrimental effects of pre-hatch exposure to chlorpyrifos on neurogenesis and several neurotransmitter systems in the chick and their reversal, using mesenchymal stem cell (MSC) transplantation. Methods: Chicken eggs were injected with the organophosphate chlorpyrifos, 10. mg/kg eggs - a dose below the threshold for dysmorphology - on incubation days (ID) 0 and 5 and subsequently the embryos were subjected to intravenous transplantation of MSC on ID 13. Results: After hatching (day 1) the expression of the neurogenesis-related genes DCX (also confirmed by immunohistochemistry), BDNF, MAP 2, FGF 2, SOX 2 and VEGF in the lateral striatum area was decreased in the exposed group (p. <0.005). Among the studied neurotransmitter systems (serotonergic, dopaminergic and cholinergic), increased gene expression was demonstrated for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) with a corresponding decrease in serotonin receptor 1A (5HTR1A) (p. <0.05); no changes in gene expression of choline transporter, PKC beta and D2 were found following chlorpyrifos exposure. Conclusion: Transplantation of MSC reversed all the neurogenic and serotonergic alterations (p. <0.01). The study of chick embryo exposure to insults with subsequent MSC therapy provides a fast and simple model for elucidating the mechanisms of both the neuroteratogenicity and the therapy, steps that are critical for progress toward therapeutic applications.

AB - Introduction: A fast and simple model which uses animals lower on the evolutionary scale is beneficial for progress in neuroteratological research. Here, we established this novel model and applied it in the study of the detrimental effects of pre-hatch exposure to chlorpyrifos on neurogenesis and several neurotransmitter systems in the chick and their reversal, using mesenchymal stem cell (MSC) transplantation. Methods: Chicken eggs were injected with the organophosphate chlorpyrifos, 10. mg/kg eggs - a dose below the threshold for dysmorphology - on incubation days (ID) 0 and 5 and subsequently the embryos were subjected to intravenous transplantation of MSC on ID 13. Results: After hatching (day 1) the expression of the neurogenesis-related genes DCX (also confirmed by immunohistochemistry), BDNF, MAP 2, FGF 2, SOX 2 and VEGF in the lateral striatum area was decreased in the exposed group (p. <0.005). Among the studied neurotransmitter systems (serotonergic, dopaminergic and cholinergic), increased gene expression was demonstrated for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) with a corresponding decrease in serotonin receptor 1A (5HTR1A) (p. <0.05); no changes in gene expression of choline transporter, PKC beta and D2 were found following chlorpyrifos exposure. Conclusion: Transplantation of MSC reversed all the neurogenic and serotonergic alterations (p. <0.01). The study of chick embryo exposure to insults with subsequent MSC therapy provides a fast and simple model for elucidating the mechanisms of both the neuroteratogenicity and the therapy, steps that are critical for progress toward therapeutic applications.

KW - Adult neurogenesis

KW - Chick model

KW - Chlorpyrifos

KW - Gene expression

KW - Mesenchymal stem cell therapy

KW - Neurotransmitter systems

KW - Pre-hatch exposure

UR - http://www.scopus.com/inward/record.url?scp=84932643846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84932643846&partnerID=8YFLogxK

U2 - 10.1016/j.ntt.2015.06.004

DO - 10.1016/j.ntt.2015.06.004

M3 - Article

C2 - 26111651

AN - SCOPUS:84932643846

VL - 50

SP - 73

EP - 81

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

ER -