Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 333 Techno Jungang Daero, Hyeonpung-Myeon, Dalseong-Gun, Daegu, 42988, Republic of Korea.
Neurometabolomics Research Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
Mol Brain. 2018 Jul 3;11(1):37. doi: 10.1186/s13041-018-0381-8.
Chronic stress is a psychologically significant factor that impairs learning and memory in the hippocampus. Insulin signaling is important for the development and cognitive function of the hippocampus. However, the relation between chronic stress and insulin signaling at the molecular level is poorly understood. Here, we show that chronic stress impairs insulin signaling in vitro and in vivo, and thereby induces deficits in hippocampal spatial working memory and neurobehavior. Corticosterone treatment of mouse hippocampal neurons in vitro caused neurotoxicity with an increase in the markers of autophagy but not apoptosis. Corticosterone treatment impaired insulin signaling from early time points. As an in vivo model of stress, mice were subjected to chronic restraint stress. The chronic restraint stress group showed downregulated insulin signaling and suffered deficits in spatial working memory and nesting behavior. Intranasal insulin delivery restored insulin signaling and rescued hippocampal deficits. Our data suggest that psychological stress impairs insulin signaling and results in hippocampal deficits, and these effects can be prevented by intranasal insulin delivery.
慢性应激是一种心理上重要的因素，会损害海马体的学习和记忆。胰岛素信号对于海马体的发育和认知功能很重要。然而，慢性应激与分子水平上的胰岛素信号之间的关系还不太清楚。在这里，我们表明慢性应激会损害体外和体内的胰岛素信号，从而导致海马体空间工作记忆和神经行为缺陷。皮质酮处理体外培养的小鼠海马神经元会引起神经毒性，自噬标志物增加，但凋亡标志物没有增加。皮质酮处理从早期时间点开始损害胰岛素信号。作为应激的体内模型，小鼠被施加慢性束缚应激。慢性束缚应激组表现出胰岛素信号下调，并出现空间工作记忆和筑巢行为缺陷。鼻内胰岛素给药恢复了胰岛素信号，并挽救了海马体的缺陷。我们的数据表明，心理应激会损害胰岛素信号，导致海马体缺陷，而这些影响可以通过鼻内胰岛素给药来预防。
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