Disturbance of oligodendrocyte differentiation in schizophrenia in relation to main hypothesis of the disease

Abstract

Increasing evidence coming from neuroimaging, molecular genetic and post-mortem studies have implicated oligodendrocyte abnormalities and compromised myelin integrity in schizophrenia. Activity-dependent myelination in adult brain is considered to be an important mechanism of neural circuit’s plasticity due to the presence of a large population of oligodendrocyte progenitor cells (OPC) in the adult CNS. Growing evidence for impairment of oligodendrocyte differentiation has been reported in the brain of schizophrenia subjects. OPC are very vulnerable inflammation, oxidative stress, and elevated glutamate levels leading to excitotoxicity. The mechanisms of prolonged suppression of oligodendrocyte differentiation caused by prenatal maternal infection or preterm birth are discussed in view of increased risk of schizophrenia, neurodevelopmental and inflammation hypotheses of the disease. The data that some neuroleptics stimulate OPC differentiation and ameliorate myelin alterations support the notion that impairment in the differentiation of OPCs contributes to oligodendrocyte abnormalities and to the pathophysiology of schizophrenia.