Stimulation of astrocytic sigma-1 receptor is sufficient to ameliorate inflammation- induced depression
Stimulation of astrocytic sigma-1 receptor is sufficient to ameliorate inflammation- induced depression
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星形细胞 sigma-1 受体的刺激足以改善炎症引起的抑郁症
DOI：
10.1016/j.bbr.2021.113344
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发表时间：
2021-05-06
影响因子：
2.7
通讯作者：
Wang, Yun
中科院分区：
文献类型：
--
作者：
Guo, Lin;Gao, Tianyu;Wang, Yun
星形胶质细胞在抑郁症的发生发展中起重要作用。sigma-1受体（sigma-1 receptor，Sig-1 R）作为抗抑郁药的一个靶点，在我们前期的研究中发现，Sig-1 R在慢性应激诱导的抑郁症中能促进星形胶质细胞的活化。然而，星形胶质细胞在炎症诱导的抑郁症中过度活化，引起了对星形胶质细胞Sig-1 R的刺激是否会在炎症诱导的抑郁症中发挥抗抑郁剂样作用的关注。我们用腺相关病毒（adenoassociated virus，AAV）特异性刺激星形胶质细胞的Sig-1 R，可显著减轻脂多糖（lipopolysaccharide，LPS）诱导的强迫游泳（forced swim test，FST）、悬尾试验（tail suspension test，TST）和蔗糖偏好试验中的抑郁样行为，并改善新物体识别试验中的记忆功能。此外，特异性刺激星形胶质细胞Sig-1 R可降低LPS诱导的抑郁症中星形胶质细胞和小胶质细胞的活化，并增加脑源性神经营养因子（BDNF）。在原代培养的星形胶质细胞中，Sig-1 R的过表达也降低了炎症处理的星形胶质细胞中IL-18、TNF-α、iNOS的表达。总之，结果表明，特异性刺激星形胶质细胞Sig-1 R改善炎症诱导的抑郁样行为，提供证据表明星形胶质细胞Sig-1 R可以代表抑郁症的可靠治疗靶点。
Astrocytes play important roles in the development of depression. As a promising target for antidepressant development, sigma-1 receptor (Sig-1R) is reported to promote activation of astrocyte in chronic stress-induced depression in our previous study. However, astrocytes are hyper-activated in inflammation-induced depression, raising concerns of whether stimulation of astrocytic Sig-1R would exert antidepressant-like effect in inflammation-induced depression. Here we reported that specific stimulation of astrocytic Sig-1R using adenoassociated virus (AAV) significantly attenuated lipopolysaccharide (LPS)- induced depressive-like behavior in the forced swim test (FST), tail suspension test (TST), sucrose preference test, and improved the memory function in novel object recognition test. Besides, specific stimulation of astrocytic Sig-1R decreased the activation of astrocyte and microglia, as well as increased brain-derived neurotrophic factor (BDNF) in LPS-induced depression. In primary cultured astrocytes, overexpression of Sig-1R also reduced the expression of IL-18, TNF-alpha, iNOS during inflammation-treated astrocyte. Taken together, the results suggest that specific stimulation of astrocytic Sig-1R ameliorates inflammation-induced depressive-like behavior, providing the evidence that astrocytic Sig-1R could represent a reliable therapeutic target for depression.