Locus coeruleus-CA1 projections are involved in chronic depressive stress-induced hippocampal vulnerability to transient global ischaemia
Locus coeruleus-CA1 projections are involved in chronic depressive stress-induced hippocampal vulnerability to transient global ischaemia
复制标题
蓝斑-CA1 投射参与慢性抑郁应激诱导的海马对短暂性全局缺血的脆弱性
DOI：
10.1038/s41467-019-10795-9
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发表时间：
2019
影响因子：
16.6
通讯作者：
Tian Bo
中科院分区：
文献类型：
--
作者：
Zhang Qian;Hu Dian Xing;He Feng;Li Chun Yang;Qi Guang Jian;Cai Hong Wei;Li Tong Xia;Ming Jie;Zhang Pei;Chen Xiao Qian;Tian Bo
抑郁症和短暂性脑缺血发作分别代表了常见的心理和神经系统疾病，并且密切相关。然而，抑郁症影响缺血发作的研究仅限于流行病学证据，抑郁症调制的缺血性损伤的神经回路仍然未知。在这里，我们发现，慢性社会失败的压力（CSDS）和慢性足电击应激（CFS）加剧CA 1神经元的损失和空间学习/记忆障碍后，短暂的短暂的全球缺血（TGI）攻击小鼠。蓝斑（LC）-酪氨酸羟化酶（TH，Th：）阳性神经元的直接输出的全脑映射显示，CSDS或CFS小鼠中LC-CA 1投射减少。此外，使用设计师受体专门激活的设计师药物（DREADDs）为基础的化学遗传学工具，我们确定，Th：LC-CA 1电路是必要的和足够的抑郁症诱导的TGI加重的结果。总之，我们认为Th：LC-CA 1通路在抑郁症诱导的TGI脆弱性中起着至关重要的作用，并为预防抑郁症相关的短暂性脑缺血发作提供了潜在的干预措施。
Depression and transient ischaemic attack represent the common psychological and neurological diseases, respectively, and are tightly associated. However, studies of depression-affected ischaemic attack have been limited to epidemiological evidences, and the neural circuits underlying depression-modulated ischaemic injury remain unknown. Here, we find that chronic social defeat stress (CSDS) and chronic footshock stress (CFS) exacerbate CA1 neuron loss and spatial learning/memory impairment after a short transient global ischaemia (TGI) attack in mice. Whole-brain mapping of direct outputs of locus coeruleus (LC)-tyrosine hydroxylase (TH, Th:) positive neurons reveals that LC-CA1 projections are decreased in CSDS or CFS mice. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determine that Th:LC-CA1 circuit is necessary and sufficient for depression-induced aggravated outcomes of TGI. Collectively, we suggest that Th:LC-CA1 pathway plays a crucial role in depression-induced TGI vulnerability and offers a potential intervention for preventing depression-related transient ischaemic attack.