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Neurotoxicol Teratol. 2015 Jul-Aug;50:73-81. doi: 10.1016/j.ntt.2015.06.004. Epub 2015 Jun 23.

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

Author information

1
The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Israel; The Hebrew University-Hadassah Medical School, Box 12272, 91120 Jerusalem, Israel. Electronic address: adi.pinkas@gmail.com.
2
Department of Molecular Biology, Ariel University, Ariel, Israel.
3
Department of Biotechnology, Hadassah Academic College, 9101001 Jerusalem, Israel.
4
The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Israel; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

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, 10mg/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

PMID:
26111651
DOI:
10.1016/j.ntt.2015.06.004
[Indexed for MEDLINE]

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