- Our paper "Depression-like Episodes in Mice Harboring mtDNA Deletions in Paraventricular Thalamus" has been published in Molecular Psychiatry.
- "Minding the brain in bipolar disorder", an Interview with Dr. Tadafumi Kato, the laboratory head, was published in RIKEN Research.
- Our new review paper, "Animal models of recurrent or bipolar depression" has been published in Neuroscience.
- Dr. Tadafumi Kato, the laboratory head, received Tsukahara Award, from Brain Science Foundation.
- A call for applications for Research Scientist Position is now open.
- 【Updated】Our paper was introduced by Science (online version), Scientific American,and Nature Medicine.
- Our paper "Increased L1 retrotransposition in the neuronal genome in schizophrenia" was accepted by Neuron. It is a collaborative study with Dept. of Molecular Psychiatry, Graduate School of Medicine, The Univ. of Tokyo, Keio Uinv., Nara Medical Univ., Brain Res. Inst.,Niigata Univ. Press release material is here.
- Our website has been renewed.
Elucidation of the neural basis of bipolar disorder based on mitochondrial dysfunction hypothesis
- Animal Model
Using neuron-specific mutant Polg1 (polymerase gamma) transgenic mice, which accumulate mitochondrial DNA (mtDNA) mutations in the brain, behavioral characteristics are examined. We found various bipolar disorder-like phenotypes in these mice. We examined the distribution of mtDNA in the mouse brain and found that mtDNA is most abundant in midbrain ventral tegmental area and substantia nigra, which contain dopaminergic neurons. We are now searching for the neuroanatomical basis of behavioral alteration of mutant Polg1 transgenic mice.
We performed exome analysis in a case with mitochondrial diseases accompanying depression and found a causative mutation in RRM2B.
Gene expression analysis of candidate genes was performed in lymphoblastoid cells of patients with bipolar disorder and control subjects, and its diagnostic value was examined. Expression levels of ANK3, RASGRP1, and POLG1 were suggested to be candidate biomarkers.
DNA methylation plays a role in long term gene expression regulation, affected by environmental factors. We study the possible roles of DNA methylation and other DNA modifications in the pathophysiology of mental disorders.
- DNA methylation difference between monozygotic twins
DNA methylation difference between lymphoblastoid cells of the monozygotic twins discordant for bipolar disorder were searched for. At first, the alteration of DNA methylation by EB virus transfection was examined. Using these data, the data in twins were analyzed, and DNA methylation difference in serotonin transporter gene was found. This finding was confirmed in a case control study, and also in postmortem brains.
- DNA methylation in the postmortem brains
We separated human postmortem brains into neuronal and non-neuronal nuclei and comprehensive DNA methylation analysis was performed. We found that neurons are globally hypomethylated, and neurons and non-neurons show distinctive features; genes expressed in astrocytes are methylated in neurons, while gene related to neuronal functions are methylated in non-neurons.