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演題詳細

Tsukahara Award Lectures


開催日 2014/9/11
時間 15:30 - 16:00
会場 Room A(Main Hall)
Chairperson(s) 山脇 成人 / Shigeto Yamawaki (広島大学大学院 医歯薬保健学研究科研究室 応用生命科学部門 精神神経医科学教室 / Department of Psychiatry and Neuroscience, Institute of Biomedical & Health Science, Hiroshima University)

双極性障害の神経生物学的研究
Neurobiological studies of bipolar disorder

  • AL-1-2
  • 加藤 忠史 / Tadafumi Kato:1 
  • 1:独立行政法人 理化学研究所 脳科学総合研究センター / RIKEN Brain Science Institute 

Bipolar disorder is one of major mental disorders characterized by recurrent mania and depression. Twin studies showed the role of genetic factors. Involvement of calcium signaling abnormality is suggested in bipolar disorder by multiple lines of evidence; association with CACNA1C and other calcium channel genes found by genome wide association studies, increased basal or activated intracellular calcium levels in blood cells, effect of lithium, a mood stabilizer, on phosphoinositide signaling, and comorbidity with Mendelian diseases caused by mutations of endoplasmic reticulum- or mitochondria-related genes (Wolfram disease, Darier's disease, and chronic progressive external ophthalmoplegia [CPEO]). Recent studies showed the role of de novo mutations or somatic mutations in the brain in neuropsychiatric diseases. We previously reported that partially deleted mitochondrial DNA (mtDNA) was accumulated in the postmortem brains of patients with bipolar disorder, and generated forebrain neuron-specific mutant Polg (mtDNA polymerase) transgenic mice accumulating deleted mtDNA in the brain. Behavioral analyses of the mice showed recurrent depression-like episodes, which responded to anti-depressive pharmacological treatments. We found that neurons accumulating mtDNA deletions are accumulated in several brain regions related to emotion regulation. This finding is now also under- investigation in postmortem brains of patients with bipolar disorder. By an integrated approach using genetics, animal models and postmortem brain analyses, neurobiological basis of bipolar disorder will be elucidated in the coming decades.

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