精神疾患の中間表現型としての未成熟歯状回(2012年度 第2回フォーラム基礎心理学のための基礎研究-網膜,遺伝子,インタフェース-)

抄録

Maturation and integration of neurons and grial cells in the hippocampus is considered to be essential for regulating endocrine, affective, and congnitive functions, and the disruption of such process may cause mental illness. Previously, we have reported that mice heterozygous for a null mutation in α-CaMKII, which has a key role in a synaptic plasticity, show abnormal behaviors related to psychiatric disorders, such as schizophrenia and bipolar disorder. In these mutant mice, almost all neurons in the dentate gyrus are at a pseudo-immature properties, whihc we referred to as "immature dentate gyrus (iDG)." To date, the iDG phenotype have been found in mustant strains including Schnurri-2 knockout, SNAP-25 mutant, and forebrain-specific calcineurin knockout mice which show similar behavioral phenotypes. In addition, both chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the maturation state of the mature neurons, resulting in the iDG phenotype in wild-type mice. Such iDG-like phenomenon was observed in the brains from patients with schizophrenia/bipolar disorder. Based on the findings, we proposed that the iDG is a potential new endophenotype of neuropsychiatric disorders. This review summarizes the behavioral abnormalities, iDG phenotype, and the implications in the pathophysiology of neuropsychiatric disorders.