Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells

Gadi Turgeman, Adi Pinkas, Theodore A. Slotkin, Matanel Tfilin, Rachel Langford, Joseph Yanai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neurobehavioral teratogenicity can be reversed with transplantation of neural stem cells. However, the usefulness of this therapy would be greatly enhanced by employing adult stem cells. In pursuit of this this goal, we developed a model that uses subventricular zone (SVZ) cells. HS/Ibg mice were exposed prenatally to chlorpyrifos on gestational days 9-18 (3 mg/kg/day, SC) in order to induce deficits in their performance in the Morris water maze test. Both the control and the exposed offspring were transplanted with SVZ cells (or vehicle) on postnatal day 35; this actually represents an allogenic transplantation, because the HS/Ibg strain is a heterogeneous stock. The transplanted cells were later observed in the host brain by DiI tracing, and their initial differentiation to cholinergic neurons and astrocytes was ascertained. On postnatal day 80, animals that had been exposed prenatally to chlorpyrifos displayed impaired Morris water maze performance, requiring more time to reach the platform. Transplantation of adult SVZ-derived neural stem cells (NSC) reversed the deficits. Applying autologous transplantation provides an important demonstration that the methodological obstacles of immunological rejection and the ethical concerns related to using embryonic stem cells may be successfully bypassed in developing stem cell therapies for neurodevelopmental disorders.

Original languageEnglish (US)
Pages (from-to)1185-1193
Number of pages9
JournalJournal of Neuroscience Research
Volume89
Issue number8
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Chlorpyrifos
Neural Stem Cells
Lateral Ventricles
Transplantation
Adult Stem Cells
Cholinergic Neurons
Water
Autologous Transplantation
Homologous Transplantation
Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Astrocytes
Stem Cells
Brain
Therapeutics

Keywords

  • Allogenic transplantation
  • Chlorpyrifos
  • Mice
  • Morris water maze
  • Neural stem cells
  • Neurobehavioral teratogenicity
  • Subventricular zone
  • Transplantation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells. / Turgeman, Gadi; Pinkas, Adi; Slotkin, Theodore A.; Tfilin, Matanel; Langford, Rachel; Yanai, Joseph.

In: Journal of Neuroscience Research, Vol. 89, No. 8, 01.08.2011, p. 1185-1193.

Research output: Contribution to journalArticle

Turgeman, Gadi ; Pinkas, Adi ; Slotkin, Theodore A. ; Tfilin, Matanel ; Langford, Rachel ; Yanai, Joseph. / Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells. In: Journal of Neuroscience Research. 2011 ; Vol. 89, No. 8. pp. 1185-1193.
@article{ac7e97fb39e5483eabea975a6de175bf,
title = "Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells",
abstract = "Neurobehavioral teratogenicity can be reversed with transplantation of neural stem cells. However, the usefulness of this therapy would be greatly enhanced by employing adult stem cells. In pursuit of this this goal, we developed a model that uses subventricular zone (SVZ) cells. HS/Ibg mice were exposed prenatally to chlorpyrifos on gestational days 9-18 (3 mg/kg/day, SC) in order to induce deficits in their performance in the Morris water maze test. Both the control and the exposed offspring were transplanted with SVZ cells (or vehicle) on postnatal day 35; this actually represents an allogenic transplantation, because the HS/Ibg strain is a heterogeneous stock. The transplanted cells were later observed in the host brain by DiI tracing, and their initial differentiation to cholinergic neurons and astrocytes was ascertained. On postnatal day 80, animals that had been exposed prenatally to chlorpyrifos displayed impaired Morris water maze performance, requiring more time to reach the platform. Transplantation of adult SVZ-derived neural stem cells (NSC) reversed the deficits. Applying autologous transplantation provides an important demonstration that the methodological obstacles of immunological rejection and the ethical concerns related to using embryonic stem cells may be successfully bypassed in developing stem cell therapies for neurodevelopmental disorders.",
keywords = "Allogenic transplantation, Chlorpyrifos, Mice, Morris water maze, Neural stem cells, Neurobehavioral teratogenicity, Subventricular zone, Transplantation",
author = "Gadi Turgeman and Adi Pinkas and Slotkin, {Theodore A.} and Matanel Tfilin and Rachel Langford and Joseph Yanai",
year = "2011",
month = "8",
day = "1",
doi = "10.1002/jnr.22631",
language = "English (US)",
volume = "89",
pages = "1185--1193",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by allographic transplantation of adult subventricular zone-derived neural stem cells

AU - Turgeman, Gadi

AU - Pinkas, Adi

AU - Slotkin, Theodore A.

AU - Tfilin, Matanel

AU - Langford, Rachel

AU - Yanai, Joseph

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Neurobehavioral teratogenicity can be reversed with transplantation of neural stem cells. However, the usefulness of this therapy would be greatly enhanced by employing adult stem cells. In pursuit of this this goal, we developed a model that uses subventricular zone (SVZ) cells. HS/Ibg mice were exposed prenatally to chlorpyrifos on gestational days 9-18 (3 mg/kg/day, SC) in order to induce deficits in their performance in the Morris water maze test. Both the control and the exposed offspring were transplanted with SVZ cells (or vehicle) on postnatal day 35; this actually represents an allogenic transplantation, because the HS/Ibg strain is a heterogeneous stock. The transplanted cells were later observed in the host brain by DiI tracing, and their initial differentiation to cholinergic neurons and astrocytes was ascertained. On postnatal day 80, animals that had been exposed prenatally to chlorpyrifos displayed impaired Morris water maze performance, requiring more time to reach the platform. Transplantation of adult SVZ-derived neural stem cells (NSC) reversed the deficits. Applying autologous transplantation provides an important demonstration that the methodological obstacles of immunological rejection and the ethical concerns related to using embryonic stem cells may be successfully bypassed in developing stem cell therapies for neurodevelopmental disorders.

AB - Neurobehavioral teratogenicity can be reversed with transplantation of neural stem cells. However, the usefulness of this therapy would be greatly enhanced by employing adult stem cells. In pursuit of this this goal, we developed a model that uses subventricular zone (SVZ) cells. HS/Ibg mice were exposed prenatally to chlorpyrifos on gestational days 9-18 (3 mg/kg/day, SC) in order to induce deficits in their performance in the Morris water maze test. Both the control and the exposed offspring were transplanted with SVZ cells (or vehicle) on postnatal day 35; this actually represents an allogenic transplantation, because the HS/Ibg strain is a heterogeneous stock. The transplanted cells were later observed in the host brain by DiI tracing, and their initial differentiation to cholinergic neurons and astrocytes was ascertained. On postnatal day 80, animals that had been exposed prenatally to chlorpyrifos displayed impaired Morris water maze performance, requiring more time to reach the platform. Transplantation of adult SVZ-derived neural stem cells (NSC) reversed the deficits. Applying autologous transplantation provides an important demonstration that the methodological obstacles of immunological rejection and the ethical concerns related to using embryonic stem cells may be successfully bypassed in developing stem cell therapies for neurodevelopmental disorders.

KW - Allogenic transplantation

KW - Chlorpyrifos

KW - Mice

KW - Morris water maze

KW - Neural stem cells

KW - Neurobehavioral teratogenicity

KW - Subventricular zone

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=79957877997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957877997&partnerID=8YFLogxK

U2 - 10.1002/jnr.22631

DO - 10.1002/jnr.22631

M3 - Article

C2 - 21520219

AN - SCOPUS:79957877997

VL - 89

SP - 1185

EP - 1193

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 8

ER -