Abstract
We hypothesized that dysfunction of mitochondria in the brain is involved in the pathophysiology of bipolar disorder (BD). We previously reported that neuron - specific mutant Polg1 (mitochondria DNA polymerase) transgenic (Tg) mice exhibited BD- like phenotypes and proposed that the Tg mice would be an animal model of bipolar disorder. We examined gene expression profiles in the brains of the Tg mice using DNA microarray analysis and the obtained data were compared with the data in the postmortem brains of patients with bipolar disorder. We found that PPIF showed similar changes. PPIF encodes cyclophilin D (CypD), a component of the mitochondrial permeability transition pore. A CypD inhibitor, NIM811, significantly improved the abnormal behavior of the Tg mice. These findings suggest that CypD is a promising target for a new drug for BD and our model mouse is useful for the development of new mood stabilizers.
