1. Academic Validation
  2. Microglial expression of GAT-1 in the cerebral cortex

Microglial expression of GAT-1 in the cerebral cortex

  • Glia. 2020 Mar;68(3):646-655. doi: 10.1002/glia.23745.
Giorgia Fattorini 1 2 Myriam Catalano 3 Marcello Melone 1 2 Carmela Serpe 3 Silvia Bassi 1 Cristina Limatola 3 4 Fiorenzo Conti 1 2
Affiliations

Affiliations

  • 1 Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, Italy.
  • 2 Center for Neurobiology of Aging, IRCCS INRCA, Ancona, Italy.
  • 3 Department of Physiology and Pharmacology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia, Rome, Italy.
  • 4 IRCCS Neuromed, Via Atinense, Pozzilli, Italy.
Abstract

Microglial cells are the immune cells of the brain that, by sensing the microenvironment, permit a correct brain development and function. They communicate with Other glial cells and with neurons, releasing and responding to a number of molecules that exert effects on surrounding cells. Among these, neurotransmitters and, in particular, gamma-aminobutyric acid (GABA) has recently gained interest in this context. We demonstrated the expression of GABA transporter 1 (GAT-1) in microglial cells both in soma and cell processes. We show that microglial cell treatment with 1,2,5,6-tetrahydro-1-[2-[[(diphenylmethylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid hydrochloride (NNC-711), a potent and selective GAT-1 inhibitor, significantly reduced Na+ -dependent GABA uptake. On the Other hand, GABA uptake was significantly increased by cell treatment with (S)-1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]-3-piperidinecarboxylic acid (SNAP-5114), a GAT-2/3 inhibitor, and this effect was completely blocked by the botulinum toxin BoNT/C1, that specifically cleaves and inactives syntaxin 1A (STX1A). Overall, these findings show that microglial cells express GAT-1 and indicate that STX1A plays an important role in the regulation of GAT-1-dependent GABA uptake in microglia.

Keywords

GABA; GABA transporter 1; microglial cells.

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