Cell type-specific epigenomic analysis of brain in a non-human primate model of depression

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K17815
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; Laboratory animal science
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Hayashi Yoshitaka 滋賀医科大学, 医学部, 助教 (10631567)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 大うつ病 / オリゴデンドロサイト / エピゲノム

Outline of Final Research Achievements

In the postmortem study of brains from patients with major depression, we found the reduction of oligodendrocyte lineage cells specifically in the prefrontal cortex of the patient brains. We hypothesized that this abnormality is caused by epigenetic changes and conducted the current study. The number of proliferating oligodendrocyte lineage cells was measured in wild-type crab-eating macaque brains and found higher numbers in the prefrontal cortex and cingulate gyrus which have been suggested to be associated with psychiatric disorders. We analyzed the brains from depression models of crab-eating macaques established by chronically treated with interferon-alpha, and found DNA methylation abnormality in the Sox10 promoter in oligodendrocyte lineage cells.

Free Research Field

脳神経科学

Academic Significance and Societal Importance of the Research Achievements

2011年に厚生労働省が特に対策を進める5大疾患に精神疾患を加えたように、精神疾患の病態解明が期待されている。これまで、神経細胞を標的とした研究が多く行われてきており、一定の成果を上げているが、未だ病因の解明には至っていない。本研究では、オリゴデンドロサイト系譜細胞を標的とし、非ヒト霊長類を用いた研究により、病態解明を目指した。脳部位によってオリゴデンドロサイト系譜細胞の増殖数が異なることや、DNAメチル化変化を見出し、今後の病態解明に繋げたい。