title: In utero PCP exposure alters oligodendrocyte differentiation and myelination in developing rat frontal cortex.
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.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 E. Clark Street, Vermillion, SD 57069, USA.
authors.forename: Josette S
authors.initials: JS
authors.lastname: Lindahl
authors.forename: Barton R
authors.initials: BR
authors.lastname: Kjellsen
authors.forename: Jamie
authors.initials: J
authors.lastname: Tigert
authors.forename: Robin
authors.initials: R
authors.lastname: Miskimins
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D011247:Pregnancy; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D004676:Myelin Basic Protein; D010622:Phencyclidine; D011509:Proteoglycans; D016194:Receptors, N-Methyl-D-Aspartate; D000099216:Chondroitin Sulfate Proteoglycan 4