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抑郁样状态下功能失调的血清素能神经元-星形胶质细胞信号传递。

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states.

机构信息

Cajal Institute, CSIC, 28002, Madrid, Spain.

PhD Program in Neuroscience, Autonoma de Madrid University-Cajal Institute, Madrid, 28029, Spain.

出版信息

Mol Psychiatry. 2023 Sep;28(9):3856-3873. doi: 10.1038/s41380-023-02269-8. Epub 2023 Sep 29.

DOI:10.1038/s41380-023-02269-8
PMID:37773446
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10730416/
Abstract

Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca signaling in MDD are poorly understood. Here, we found that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic Ca dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated Ca signaling in mPFC astrocytes, and aberrant 5-HT-driven synaptic plasticity in layer 2/3 mPFC neurons. Downregulation of astrocyte Ca signaling in naïve animals mimicked the synaptic deficits found in Cort-mice. Remarkably, boosting astrocyte Ca signaling with Gq-DREADDS restored to the control levels mood and cognitive abilities in Cort-mice. This study highlights the important role of astrocyte Ca signaling for homeostatic control of brain circuits and behavior, but also reveals its potential therapeutic value for depressive-like states.

摘要

星形胶质细胞在大脑稳态中发挥着至关重要的作用，是神经元和突触生理学的调节因子。在重度抑郁症（MDD）患者中发现了星形胶质细胞的改变；然而，MDD 中星形胶质细胞 Ca 信号的后果还知之甚少。在这里，我们发现皮质酮处理的幼年小鼠（Cort 小鼠）在静息状态和社交互动期间，其 mPFC 中的星形胶质细胞 Ca 动力学发生改变，与行为改变一致。此外，Cort 小鼠显示 mPFC 星形胶质细胞中 5-羟色胺（5-HT）介导的 Ca 信号减少，以及 mPFC 神经元中第 2/3 层异常的 5-HT 驱动的突触可塑性。在未处理的动物中下调星形胶质细胞 Ca 信号，模拟了在 Cort 小鼠中发现的突触缺陷。值得注意的是，使用 Gq-DREADDS 增强星形胶质细胞 Ca 信号可将 Cort 小鼠的情绪和认知能力恢复到对照水平。这项研究强调了星形胶质细胞 Ca 信号在大脑回路和行为的稳态控制中的重要作用，但也揭示了其在抑郁样状态下的潜在治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/c21518eedefb/41380_2023_2269_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/ea38c03f0cf2/41380_2023_2269_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/c21518eedefb/41380_2023_2269_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/ea38c03f0cf2/41380_2023_2269_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/657160210261/41380_2023_2269_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/c752da50cecb/41380_2023_2269_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/4e3f383cf8c3/41380_2023_2269_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/10730416/c21518eedefb/41380_2023_2269_Fig5_HTML.jpg

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