Transmembrane Protein 108 Inhibits the Proliferation and Myelination of Oligodendrocyte Lineage Cells in the Corpus Callosum

Abstract

Background: Abnormal white matter is a common neurobiological change in bipolar disorder, and dysregulation of myelination in oligodendrocytes is the cause. Transmembrane protein 108 (Tmem108), as a susceptible gene of bipolar disorder, is expressed higher in oligodendrocyte lineage cells than any other lineage cells in the central nervous system. Moreover, Tmem108 mutant mice exhibit mania-like behaviors, belonging to one of the signs of bipolar disorder. However, it is unknown whether Tmem108 regulates myelination of the oligodendrocytes.Results: Tmem108 expression in the corpus callosum decreased with the development, and hypermyelination of the corpus callosum was found in Tmem108 mutant mice, accompanying high expression of myelin basic protein. Strikingly, both oligodendrocyte progenitor cell proliferation and oligodendrocyte myelination were enhanced in the mutant mice. Furthermore, the mutant mice exhibited mania-like behavior after acute restraint stress and were susceptible to drug-induced epilepsy. Conclusions: Tmem108 inhibited oligodendrocyte progenitor cell proliferation and mitigated oligodendrocyte maturation in the corpus callosum, which may also provide a new role of Tmem108 involving bipolar disorder pathogenesis.