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Updated: Jul 3, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
In utero PCP exposure alters oligodendrocyte differentiation and myelination in developing rat frontal cortex
Josette S Lindahl1, Barton R Kjellsen, Jamie Tigert
1Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 E. Clark Street, Vermillion, SD 57069, USA.
Insights
Prenatal NMDA receptor blockade with phencyclidine (PCP) in rats reduces oligodendrocyte progenitor cells. This leads to immature cells and fewer mature oligodendrocytes, impacting myelin development and potentially contributing to neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuropharmacology
Background:
- Neurodevelopmental disorders like schizophrenia and autism are linked to white matter abnormalities.
- Glutamate signaling and NMDA receptors are crucial for central nervous system (CNS) development.
- Oligodendrocytes, the myelin-producing cells, are implicated in these disorders.
Purpose of the Study:
- To investigate how modulating the glutamate system affects oligodendrocyte maturation.
- To examine the impact of prenatal NMDA receptor blockade on oligodendrocyte development.
Main Methods:
- Developing rats were exposed prenatally to phencyclidine (PCP) to block NMDA receptors.
- Postnatal analysis of oligodendrocyte development using cell-stage specific markers.
- Quantification of marker proteins for neurons, astrocytes, and oligodendrocytes at various developmental stages.
Main Results:
- Prenatal PCP exposure decreased early oligodendrocyte progenitor cell markers.
- Elevated levels of intermediate, immature oligodendrocyte markers were observed.
- A subsequent decrease in late-stage markers for mature, myelinating oligodendrocytes was found.
Conclusions:
- Prenatal NMDA receptor blockade impairs oligodendrocyte progenitor cell numbers.
- Surviving oligodendrocytes are arrested at an immature stage, hindering differentiation.
- This suggests a mechanism linking glutamate system dysfunction to white matter abnormalities in neurodevelopmental disorders.
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.
