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
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
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
U2 - 10.1016/j.ntt.2015.06.004
DO - 10.1016/j.ntt.2015.06.004
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C2 - 26111651
AN - SCOPUS:84932643846
SN - 0892-0362
VL - 50
SP - 73
EP - 81
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
ER -