Searching for the Causes of Bipolar Disorder: Mitochondrial Dysfunction Hypothesis and Beyond Tadafumi Kato 1 1Department of Psychiatry and Behavioral Science, Juntendo University Keyword: 双極性障害 , カルシウム , ミトコンドリア機能障害 , 視床室傍核 , bipolar disorder , calcium , mitochondrial dysfunction , paraventricular thalamic nucleus pp.359-367
Published Date 2021/4/1
DOI https://doi.org/10.11477/mf.1416201769
  • Abstract
  • Look Inside
  • Reference


Although the involvement of genomic factors in bipolar disorder is clear, its neural basis remains a question. We proposed the mitochondrial dysfunction hypothesis of bipolar disorder in 2000 and have since been testing it. Our results showed that mitochondrial DNA (mtDNA) polymorphisms affected mitochondrial Ca2+ concentration, and mitochondrial Ca2+ uptake and intracellular Ca2+ signaling were altered. Spontaneous repetitive depressive episodes were seen in mice in which mtDNA mutations accumulated in the brain (mutant Polg transgenic mice). We searched for the brain regions with the accumulation of mutant mtDNA in these mice, and found that it was most abundant in the paraventricular nucleus of the thalamus (PVT). Neural circuit manipulation of the PVT caused similar repetitive hypoactive episodes, suggesting that the PVT may be involved in causing bipolar disorder.

Copyright © 2021, Igaku-Shoin Ltd. All rights reserved.


電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院