Olanzapine stimulates proliferation but inhibits differentiation in rat oligodendrocyte precursor cell cultures

Abstract

In the developing brain, oligodendrocyte progenitor cells (OPCs) proliferate, migrate, and differentiate into mature oligodendrocytes (OLs) capable of myelinating axons. Recently, OPCs have been identified as an abundant and widespread population in the adult as well as in the developing animal. Current research indicates that these OPCs in the adult brain can proliferate and differentiate into myelinating OLs, albeit with different potentialities from those in developing animals. Multiple lines of evidence, from neuroimaging, postmortem, and genetic association studies, have implicated OL and myelin dysfunction in the pathogenesis of schizophrenia. If altered OL function is involved in pathogenesis, OPCs may thus respond to antipsychotic drugs during the recovery process. In the present study, we used primary OPC cultures from optic nerve of newborn Wistar rat pups to investigate the direct effects of haloperidol (HPD; a typical antipsychotic) and olanzapine (OLZ; an atypical antipsychotic) on the proliferation and differentiation of OPCs. Our results showed that 1) OLZ treatment significantly increased the number of viable OPCs when compared to HPD treatment at relatively high concentrations, 2) OLZ treatment suppressed the expression of myelin basic protein (MBP), and to a greater extent than HPD treatment, and 3) these pharmacological effects may be mediated via the ERK signaling pathway. Our findings suggest a glial mechanism for the antipsychotic action of OLZ, and a role for oligodendrocyte-lineage cells in the pathogenesis and treatment of schizophrenia.