研究人员发现，神经元活动诱导星形胶质细胞广泛的转录上调和下调，突出表现在Slc22a3是一个活动诱导的星形胶质细胞基因，它编码神经调节剂转运体Slc22a3并调节小鼠嗅球的感觉处理。星形胶质细胞Slc22a3的缺失降低了星形胶质细胞中血清素的水平，导致组蛋白血清素化的改变。星形胶质细胞中组蛋白羟化的抑制减少了γ-氨基丁酸（GABA）生物合成基因的表达和GABA释放，最终导致嗅觉障碍。这项研究揭示了神经元活动协调了星形胶质细胞的转录和表观基因组反应，同时说明了星形胶质细胞如何处理神经调节输入，为感觉处理把关神经递质释放的新机制。
据悉，神经元活动驱动了神经元内基因表达的改变，但它如何在运作的回路中指导邻近星形胶质细胞的转录和表观基因组的变化还不清楚。
附：英文原文
Title: Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation
Author: Debosmita Sardar, Yi-Ting Cheng, Junsung Woo, Dong-Joo Choi, Zhung-Fu Lee, Wookbong Kwon, Hsiao-Chi Chen, Brittney Lozzi, Alexis Cervantes, Kavitha Rajendran, Teng-Wei Huang, Antrix Jain, Benjamin R. Arenkiel, Ian Maze, Benjamin Deneen
Issue&Volume: 2023-06-16
Abstract: Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. We found that neuronal activity induces widespread transcriptional up-regulation and down-regulation in astrocytes, highlighted by the identification of Slc22a3 as an activity-inducible astrocyte gene that encodes neuromodulator transporter Slc22a3 and regulates sensory processing in the mouse olfactory bulb. Loss of astrocytic Slc22a3 reduced serotonin levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduced the expression of γ-aminobutyric acid (GABA) biosynthetic genes and GABA release, culminating in olfactory deficits. Our study reveals that neuronal activity orchestrates transcriptional and epigenomic responses in astrocytes while illustrating new mechanisms for how astrocytes process neuromodulatory input to gate neurotransmitter release for sensory processing.
DOI: ade0027
Source: https://www.science.org/doi/10.1126/science.ade0027