Di Palma, Michael and Catalano, Myriam and Serpe, Carmela and De Luca, Mariassunta and Monaco, Lucia and Kunzelmann, Karl and Limatola, Cristina and Conti, Fiorenzo and Fattorini, Giorgia (2023) Lipopolysaccharide augments microglial GABA uptake by increasing GABA transporter-1 trafficking and bestrophin-1 expression. GLIA, 71 (11). pp. 2527-2540. ISSN 0894-1491, 1098-1136
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; RECEPTORS; NEUROINFLAMMATION; CORTEX; TRANSMISSION; ACTIVATION; ASTROCYTES; CELLS; GAMMA; INHIBITION; bestrophin-1; GABA; GABA transporter 1; inflammation; LPS; microglial cells |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2024 09:20 |
| Last Modified: | 19 Mar 2024 09:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60323 |
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