抄録
Bipolar disorder is one of major mental disorders affecting about 1% of the population. Lithium, a mood stabilizer, is known to neuroprotective effect. MRI studies showed increased incidence of white matter hyperintensity. Blood cells of patients with bipolar disorder. These findings suggest that bipolar disorder is characterized by vulnerability or impaired resilience at the cellular level. We proposed the mitochondrial dysfunction hypothesis of bipolar disorder based on several findings in patients with bipolar disorder such as abnormal energy metabolism in the brain and abnormal mitochondrial DNA in the postmortem brains. This hypothesis may explain the molecular basis of such abnormality at the cellular level in bipolar disorder. Other groups are also studying the possible role of mitochondrial dysfunction in bipolar disorder. To verify the mitochondrial dysfunction hypothesis, we produced transgenic mice that accumulate abnormal mitochondrial DNA in the brain by introducing a mutation in the gene that encodes an enzyme which synthesizes mitochondrial DNA, called POLG. The wheel running activity of the transgenic mice changed periodically following the estrous cycle. The periodic activity change in mutant mice was improved by lithium, a mood stabilizer. Mitochondrial dysfunction is not specific to bipolar disorder, but common to several diseases such as Parkinson's disease or diabetes mellitus. This model mouse may be useful to identify the neural systems responsible for bipolar disorder. [J Physiol Sci. 2008;58 Suppl:S15]
