Journal
SCHIZOPHRENIA RESEARCH
Volume 187, Issue -, Pages 62-66Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2016.10.037
Keywords
Bipolar disorder; Mitochondrial DNA; Calcium; Paraventricular thalamic nucleus; Animal model
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) [24116005, 24249063]
- Japan Agency for Medical Research and Development (AMED)
- Grants-in-Aid for Scientific Research [24116005] Funding Source: KAKEN
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Bipolar disorder is one of two major psychotic disorders together with schizophrenia and causes severe psychosocial disturbance. Lack of adequate animal models hampers development of new mood stabilizers. We proposed a mitochondrial dysfunction hypothesis and have been studying the neurobiology of bipolar disorder based on this hypothesis. We showed that deletions of mitochondrial DNA (Delta mtDNA) play a pathophysiological role at least in some patients with bipolar disorder possibly by affecting intracellular calcium regulation. Mutant polymerase gamma transgenic mice that accumulate Delta mtDNA in the brain showed recurrent spontaneous depression-like episodes which were prevented by a serotonin-selective reuptake inhibitor and worsened by lithium withdrawal. The animal model would be useful to develop new mood stabilizers. (C) 2016 The Author. Published by Elsevier B.V.
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