Laboratory for Molecular Dynamics of Mental Disorders
Laboratory Head
Tadafumi KATO (M.D., Ph.D.)
The goal of this team is to clarify the molecular basis of bipolar disorder, one of two major mental disorders. Bipolar disorder may be caused by altered intracellular calcium signaling. In this study, mitochondrial calcium regulation abnormality will be characterized using cultured cells, autopsied brains derived from patients, and animal models. We recently identified that endoplasmic reticulum (ER) stress signaling plays an important role in the pathophysiology of bipolar disorder by analyzing gene expressions in monozygotic twins discordant for bipolar disorder. We are now studying the role of ER stress signaling in mental function. We are also searching for DNA methylation abnormalities as a candidate mechanism for discordance of twins, and we study possible significance of DNA methylation abnormality in mental disorders. Altogether, etiology of bipolar disorder will be elucidated and new diagnostic examination and treatment will be developed.
- Mitochondria and endoplasmic reticulum dysfunction in bipolar disorder
- Epigenetic analysis of mental disorders
- January 19, 2007
- Challenging bipolar disorder
- Kubota, M., Kasahara, T., Iwamoto, K., Komori, A., Ishiwata, M., Miyauchi, T., and Kato, T.:
"Therapeutic implications of down-regulation of cyclophilin D in bipolar disorder."
International Journal of Neuropsychopharmacology 13: 1355-1368 (2010). - Kasahara T, Abe K, Mekada K, Yoshiki A, Kato T:
"Genetic variation of melatonin productivity in laboratory mice under domestication."
Proceedings of the National Academy of Sciences of the United States of America 107: 6412-6417 (2010) - Kuratomi, G., Iwamoto, K., Bundo, M., Kusumi, I., Kato, N., Iwata, N., Ozaki, N., and Kato, T.:
"Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins."
Molecular Psychiatry 13, 429-441 (2008). - Oldham, M.C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., and Geschwind, D.H.:
"Functional organization of the transcriptome in human brain."
Nature Neuroscience 11, 1271-1282 (2008). - Kato T.:
"Molecular neurobiology of bipolar disorder: a disease of "mood stabilizing neurons""
Trends in Neuroscience 31, 495-503 (2008). - Hayashi, A., Kasahara, T., Iwamoto, K., Ishiwata, M., Kametani, M., Kakiuchi, C., Furuichi, T., and Kato T.:
"The role of BDNF-induced Xbp1 splicing during brain development."
Journal of Biological Chemistry 282, 34525-34534 (2007). - Kasahara, T., Kubota, M., Miyauchi, T., Noda, Y., Mouri, A., Nabeshima, T., and Kato, T.:
"Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes"
Molecular Psychiatry, 11, 577-593 (2006). - Kubota, M., Kasahara, T., Nakamura, T., Ishiwata, M., Miyauchi, T., and Kato, T.:
"Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial dna defects"
Journal of Neuroscience, 26, 12314-24 (2006). - Iwamoto, K., Bundo, M., and Kato, T.:
"Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis"
Human Molecular Genetics, 14, 241-53 (2005). - Kakiuchi, C., Iwamoto, K., Ishiwata, M., Bundo, M., Kasahara, T., Kusumi, I., Tsujita, T., Okazaki, Y., Nanko, S., Kunugi, H., Sasaki, T., and Kato, T.:
"Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder"
Nature Genetics, 35, 171-175 (2003).