Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes

T. Kasahara, M. Kubota, T. Miyauchi, Y. Noda, A. Mouri, T. Nabeshima, T. Kato

研究成果: ジャーナルへの寄稿学術論文査読

146 被引用数 (Scopus)

抄録

There is no established genetic model of bipolar disorder or major depression, which hampers research of these mood disorders. Although mood disorders are multifactorial diseases, they are sometimes manifested by one of pleiotropic effects of a single major gene defect. We focused on chronic progressive external ophthalmoplegia (CPEO), patients with which sometimes have comorbid mood disorders. Chronic progressive external ophthalmoplegia is a mitochondrial disease, which is accompanied by accumulation of mitochondrial DNA (mtDNA) deletions caused by mutations in nuclear-encoded genes such as POLG (mtDNA polymerase). We generated transgenic mice, in which mutant POLG was expressed in a neuron-specific manner. The mice showed forebrain-specific defects of mtDNA and had altered monoaminergic functions in the brain. The mutant mice exhibited characteristic behavioral phenotypes, a distorted day-night rhythm and a robust periodic activity pattern associated with estrous cycle. These abnormal behaviors resembling mood disorder were worsened by tricyclic antidepressant treatment and improved by lithium, a mood stabilizer. We also observed antidepressant-induced mania-like behavior and long-lasting irregularity of activity in some mutant animals. Our data suggest that accumulation of mtDNA defects in brain caused mood disorder-like mental symptoms with similar treatment responses to bipolar disorder. These findings are compatible with mitochondrial dysfunction hypothesis of bipolar disorder.

本文言語英語
ページ(範囲)577-593
ページ数17
ジャーナルMolecular Psychiatry
11
6
DOI
出版ステータス出版済み - 06-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 精神医学および精神衛生
  • 細胞および分子神経科学

フィンガープリント

「Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル