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

12 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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