Elucidation of causative neural circuit of bipolar disorder

2016 Fiscal Year Final Research Report

• Project Area: Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels.
• Project/Area Number: 24116005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kato Tadafumi 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (30214381)
• Co-Investigator(Kenkyū-buntansha): 鵜飼 渉 札幌医科大学, 医学部, 講師 (40381256)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: うつ病 / 双極性障害 / ミトコンドリアDNA / 視床室傍核

Outline of Final Research Achievements

Because mitochondrial disease frequently accompanies bipolar disorder, we developed a model mouse carrying mutant Polg, a causative gene of mitochondrial diseases. The mice showed recurrent spontaneous episodes satisfying the clinical criteria of major depression that responded to anti-depressive treatments and showed alteration of corticosteroid. We identified that mutant mitochondrial DNA is accumulated in paraventricular thalamic nucleus (PVT). Inhibition of neural transmission of PVT neurons caused similar episodes in mice. Cells with mitochondrial dysfunction were found also in paraventricular region of the postmortem brains of patients with mitochondrial disease and mood symptoms. The present findings are expected to lead to development of new mood stabilizers and diagnostic methods.

Free Research Field

神経科学、精神医学