Transmembrane protein 108 inhibits the proliferation and myelination of oligodendrocyte lineage cells in the corpus callosum

Mol Brain. 2022 Apr 11;15(1):33. doi: 10.1186/s13041-022-00918-7.

Abstract

Background: Abnormal white matter is a common neurobiological change in bipolar disorder, and dysregulation of myelination in oligodendrocytes (OLs) is the cause. Transmembrane protein 108 (Tmem108), as a susceptible gene of bipolar disorder, is expressed higher in OL 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 the myelination of the OLs.

Results: Tmem108 expression in the corpus callosum decreased with the development, and OL progenitor cell proliferation and OL myelination were enhanced in the mutant mice. Moreover, the mutant mice exhibited mania-like behavior after acute restraint stress and were susceptible to drug-induced epilepsy.

Conclusions: Tmem108 inhibited OL progenitor cell proliferation and mitigated OL maturation in the corpus callosum, which may also provide a new role of Tmem108 involving bipolar disorder pathogenesis.

Keywords: Bipolar disorder (BD); Corpus callosum (CC); Myelination; Oligodendrocyte (OL); Tmem108.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Cell Proliferation
  • Corpus Callosum*
  • Mania
  • Mice
  • Myelin Sheath / metabolism
  • Oligodendroglia / metabolism
  • White Matter*