Microglial expression of GAT-1 in the cerebral cortex

Giorgia Fattorini, Myriam Catalano, Marcello Melone, Carmela Serpe, Silvia Bassi, Cristina Limatola, Fiorenzo Conti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)646-655
Number of pages10
JournalGLIA
Volume68
Issue number3
DOIs
Publication statusE-pub ahead of print - 2019

Keywords

  • GABA
  • GABA transporter 1
  • microglial cells

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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