うつ病発症脆弱性と養育環境 : ラットの母子分離と学習性無力試験を用いた分子生物学的研究の成果から(心理学実験法の基礎的・臨床的汎用性を考える-精神医学・社会心理学のストレス脆弱性研究から-,第25回大会 シンポジウム2)

抄録

Numerous epidemiological studies in psychiatry demonstrate that an early adversity is a major risk factor for depression in adulthood. Several rodent studies reveal that neonatal isolation, maternal separation, and low maternal care induce the hyperactivation of the hypothalamo-pituitary-adrenal (HPA) axis in response to restraint stress in adulthood. Since the activation of the HPA axis plays an important role in the pathophysiology of depression, it is conceivable that the enhanced response of the HPA axis to adulthood stress induced by early adversities may be involved in the increased susceptibility to depression. We examined the influence of neonatal isolation (NI) on the susceptibility to learned helplessness (LH),an animal model of depression, in adult rats. In addition, we examined the difference of gene expression profiles in the hippocampus between the NI+LH and non-NI+non-LH rats to elucidate the molecular mechanism for the enhanced susceptibility to depression induced by an early adversity. Behavioral analysis showed that the prevalence of LH in the rats subjected to NI was significantly higher than that in the rats without NI. Molecular analysis indicated that the significant decrease in the hippocampal level of LIMK-1 was associated with the increased susceptibility to depression found in the rats subjected to NI. These findings suggest that the deceased expression of LIMK-1 may induce the morphological and functional change in the hippocampus, and subsequently increase the susceptibility to depression in response to adulthood stress.