Abstract
Alterations in myelin, the protective and insulating sheath surrounding axons, affect brain function, as is evident in demyelinating diseases where the loss of myelin leads to cognitive and motor dysfunction. Recent evidence suggests that changes in myelination, including both hyper- and hypo-myelination, may also play a role in numerous neurological and psychiatric diseases. Protecting myelin and promoting remyelination is thus crucial for a wide range of disorders. Oligodendrocytes (OLs) are the cells that generate myelin, and oligodendrogenesis, the creation of new OLs, continues throughout life and is necessary for myelin plasticity and remyelination. Understanding the regulation of oligodendrogenesis and myelin plasticity within disease contexts is, therefore, critical for the development of novel therapeutic targets. In our companion manuscript, we review literature demonstrating that multiple hormone classes are involved in the regulation of oligodendrogenesis under physiological conditions. The majority of hormones enhance oligodendrogenesis, increasing oligodendrocyte precursor cell differentiation and inducing maturation and myelin production in OLs. Thus, hormonal treatments present a promising route to promote remyelination. Here, we review the literature on hormonal regulation of oligodendrogenesis within the context of disorders. We focus on steroid hormones, including glucocorticoids and sex hormones, peptide hormones such as insulin-like growth factor 1, and thyroid hormones. For each hormone, we describe whether they aid in OL survival, differentiation, or remyelination, and we discuss their mechanisms of action, if known. Several of these hormones have yielded promising results in both animal models and in human conditions; however, a better understanding of hormonal effects, interactions, and their mechanisms will ultimately lead to more targeted therapeutics for myelin repair.
Highlights
Many neurological disorders are characterized by changes in myelin, the protective and insulating sheath surrounding axons
Similar findings are observed in vivo, where progesterone and nestorone increase the density of oligodendrocyte precursor cells (OPCs) and mature OLs, and enhance the formation of myelin proteins such as PLP and myelin basic protein (MBP) in cuprizone demyelination models [93,112]
Future work could address this by investigating regional heterogeneity of the effects of insulin and insulin-like growth factor 1 (IGF-1) signaling on brain myelination, as well as relating insulin action to myelination in animal models of obesity or diabetes
Summary
Many neurological disorders are characterized by changes in myelin, the protective and insulating sheath surrounding axons. These anilination of OLs under physiological conditions [33] In line with their effects on oligodendrogenesis, stress hormones such as GCs, and sex hormones such as estrogens, progestogens, and androgens, are associated with MS and other myelin related diseases and may aid in some aspects of myelin repair [37,38,39]. We will describe the effects of classic steroid hormones, peptide hormones, and THs. For each category, we will note the hormone’s effects on animal models characterized by impaired myelination, and we will discuss their relevance to findings in human disorders. We advocate for more extensive research into hormones as a potential therapeutic target for myelin repair
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