Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation

J Pharmacol Sci. 2015 Jan;127(1):145-9. doi: 10.1016/j.jphs.2014.09.002. Epub 2014 Oct 2.

Abstract

The extracellular L-glutamate (L-Glu) concentration is elevated in neuroinflammation, thereby causing excitotoxicity. One of the mechanisms is down-regulation of astrocyte L-Glu transporters. Some antidepressants have anti-inflammatory effects. We therefore investigated effects of various antidepressants on the down-regulation of astrocyte L-Glu transporters in the in vitro neuroinflammation model. Among these antidepressants, only paroxetine was effective. We previously demonstrated that the down-regulation of astrocyte L-Glu transporters was caused by L-Glu released from activated microglia. We here clarified that only paroxetine inhibited L-Glu release from microglia. This is the novel action of paroxetine, which may bring advantages on the therapy of neuroinflammation.

Keywords: Inflammation; L-glutamate; Paroxetine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System X-AG / metabolism*
  • Antidepressive Agents / pharmacology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cells, Cultured
  • Down-Regulation / drug effects*
  • Glutamic Acid / metabolism
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Lipopolysaccharides
  • Microglia / drug effects*
  • Microglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Paroxetine / pharmacology*

Substances

  • Amino Acid Transport System X-AG
  • Antidepressive Agents
  • Lipopolysaccharides
  • Glutamic Acid
  • Paroxetine