In utero PCP exposure alters oligodendrocyte differentiation and myelination in developing rat frontal cortex

Josette S. Lindahl, Barton R. Kjellsen, Jamie Tigert, Robin Miskimins

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Several neurodevelopmental disorders, including schizophrenia, autism, ADD/ADHD and dyslexia are believed to originate during gestation and involve white matter abnormalities. Modulation of glutamate environments and glutamate receptors has also been implicated in alteration of oligodendrocytes, the myelin forming cells of the CNS. To begin to understand how modulation of the glutamate system affects the maturation of oligodendrocytes, developing rats were subjected to prenatal blockade of the NMDA receptor with phencyclidine (PCP). Oligodendrocyte development and differentiation were then examined postnatally by measuring markers for early, middle and late stage cells. The results indicate that, while the level of marker proteins for neurons and astrocytes remains the same, early oligodendrocyte progenitor cell markers are decreased in rat brains prenatally exposed to PCP. Labeling of cells of intermediate, immature cell stages is elevated. Late stage markers for myelinating oligodendrocytes are subsequently decreased. These data suggest that prenatal NMDA receptor blockade reduces the level of progenitors and that the surviving cells are arrested at an immature stage. This premature arrest appears to result in fewer fully differentiated, mature oligodendrocytes that are capable of producing myelin. These results have interesting implications for the role of glutamate and glutamate receptors in white matter abnormalities in neurodevelopmental disorders.

Original languageEnglish (US)
Pages (from-to)137-147
Number of pages11
JournalBrain Research
Volume1234
DOIs
StatePublished - Oct 9 2008

Keywords

  • Glutamate excitotoxicity
  • Myelination
  • NMDA receptor
  • Neurodevelopment

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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