小胶质细胞
加巴能
gaba转运蛋白
γ-氨基丁酸
细胞生物学
生物
γ-氨基丁酸受体
脂多糖
下调和上调
先天免疫系统
神经递质
谷氨酸受体
药理学
炎症
抑制性突触后电位
神经科学
受体
生物化学
免疫学
基因
作者
Michael Di Palma,Myriam Catalano,Carmela Serpe,Mariassunta De Luca,Lucía Monaco,Karl Kunzelmann,Cristina Limatola,Fiorenzo Conti,Giorgia Fattorini
出处
期刊:Glia
[Wiley]
日期:2023-07-10
卷期号:71 (11): 2527-2540
摘要
Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, affects numerous immune cell functions. Microglia, the brain's resident innate immune cells, regulate GABA signaling through GABA receptors and express the complete GABAergic machinery for GABA synthesis, uptake, and release. Here, the use of primary microglial cell cultures and ex vivo brain tissue sections allowed for demonstrating that treatment with lipopolysaccharide (LPS) increased microglial GABA uptake as well as GABA transporter (GAT)-1 trafficking. This effect was not entirely abolished by treatment with GAT inhibitors (GAT-Is). Notably, LPS also induced microglial upregulation of bestrophin-1 (BEST-1), a Ca2+ -activated Cl- channel permeable to GABA. Combined administration of GAT-Is and a BEST-1 inhibitor completely abolished LPS-induced microglial GABA uptake. Interestingly, increased microglial GAT-1 membrane turnover via syntaxin 1A was detected in LPS-treated cultures after BEST-1 blockade. Altogether, these findings provided evidence for a novel mechanism through which LPS may trigger the inflammatory response by directly altering microglial GABA clearance and identified the GAT-1/BEST-1 interplay as a potential novel mechanism involved in brain inflammation.
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