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The role of distinct hippocampal calbindin neurons in modulating individual susceptibility to early life stress

不同海马钙结合蛋白神经元在调节个体对早期生活压力的易感性中的作用

基本信息

批准号：
391584407
负责人：
Privatdozent Dr. Mathias V. Schmidt, Ph.D.
金额：
--
依托单位：
Department of Neurobiology
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2018
资助国家：
德国
起止时间：
2017-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/391584407?language=en
关键词：
role distinct hippocampal calbindin neurons

项目摘要

Early-life stress is a major risk factor for psychiatric disorders including major depressive disorder. However, the neurobiological mechanisms underlying the deleterious effects of early-life stress remain to be elucidated. The Chinese and German research teams applying for this project have been collaborating on the mechanistic studies of the neurobiology of early-life stress, and have accumulated solid and exciting data. The two teams have jointly published over 10 papers in internationally renowned journals including Nature Neuroscience, Biological Psychiatry and Neuropsychopharmacology. This project focuses on calbindin, a calcium-binding protein closely related to neural plasticity and implicated in psychiatric disorders. Combining chemogenetic, molecular, morphological, pharmacological, and behavioral approaches, this project aims to reveal the regulation of hippocampal calbindin protein expression and the activity of calbindin-expressing neuronal subpopulations by key stress mediators especially the GR-FKBP51 and CRHR1-nectin-3 systems. Moreover, the involvement of distinct hippocampal calbindin-expressing neuronal subpopulations in early-life stress-impaired synaptic plasticity as well as emotional and cognitive behavior will be dissected. This study will shed new light on the underlying mechanisms of stress-related psychiatric disorders and the development of therapeutic targets.

早期生活压力是精神疾病包括重度抑郁症的主要危险因素。然而，早期生活压力的有害影响的神经生物学机制仍有待阐明。申请该项目的中德研究团队一直在合作开展早期生活应激的神经生物学机制研究，积累了扎实而令人振奋的数据。两个团队在Nature Neuroscience、Biological Psychiatry和Neuropsychopharmacology等国际知名期刊上联合发表了10多篇论文。该项目的重点是钙结合蛋白，一种与神经可塑性密切相关的钙结合蛋白，并与精神疾病有关。结合化学遗传学，分子，形态学，药理学和行为学的方法，该项目旨在揭示调节海马钙结合蛋白的蛋白表达和钙结合蛋白表达的神经元亚群的活性的关键应激介质，特别是GR-FKBP 51和CRHR 1-nectin-3系统。此外，参与不同的海马钙结合蛋白表达神经元亚群在早期生活中的压力受损的突触可塑性，以及情绪和认知行为将被解剖。这项研究将为应激相关精神障碍的潜在机制和治疗靶点的开发提供新的思路。