Pregnancy, prolactin and white matter regeneration

Abstract

New myelinating oligodendrocytes are continuously generated in the white matter of the uninjured adult CNS by oligodendrocyte precursor cells (OPCs) and neural stem cells (NSCs). Currently, little is known about the function of these new cells or the physiological processes that regulate their generation and differentiation. Importantly, new oligodendrocytes are able to contribute to the endogenous repair of white matter damage. Thus, a major biological and biomedical interest in the regulatory mechanisms governing their generation in the adult brain has arisen. Here I discuss work that demonstrates that hormonal changes during pregnancy promote increased OPC proliferation and oligodendrocyte production in the maternal CNS. We found that the maternal increase in oligodendrocyte production is associated with a significantly enhanced ability to regenerate white matter damage. Prolactin (PRL) signaling is both necessary and sufficient for the pregnancy-induced increase in OPC proliferation, and most strikingly, PRL treatments mimic the regenerative effects of pregnancy and promote white matter repair and remyelination in virgin females. I consider the implications of this work for our understanding of maternal adaptations to pregnancy and for the treatment of Multiple Sclerosis.