In vitro activation of GAT1 transporters expressed in spinal cord gliosomes stimulates glutamate release that is abnormally elevated in the SOD1/G93A(+) mouse model of amyotrophic lateral sclerosis

Journal of Neurochemistry
Marco MilaneseGiambattista Bonanno

Abstract

The effect of GABA on glutamate release from astrocytes has been studied in healthy mice and in a murine transgenic model of amyotrophic lateral sclerosis (ALS), using mouse spinal cord gliosomes labeled with [(3)H]d-aspartate ([(3)H]d-ASP). GABA concentration-dependently evoked the release of [(3)H]d-ASP. The effect of GABA was not mimicked by GABA(A) or GABA(B) receptor agonists or counteracted by antagonists, excluding receptor involvement. However, it was prevented by the GABA transport inhibitor N-(4,4-phenyl-3-butenyl)-nipecotic acid (SKF 89976A), suggesting participation of GABA transporters type 1 (GAT1) placed on glutamate-releasing astrocyte-derived gliosomes. Accordingly, GAT1 co-expressed with glutamate-aspartate transporter (GLAST) and glutamate transporter type 1 (GLT1) in the majority of glial particles. [(3)H]d-aspartate release was Ca(2+)-independent and not blocked by the glutamate uptake inhibitor dl-threo-b-benzyloxyaspartic acid (dl-TBOA); instead, it was abrogated by the anion channel blockers niflumic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). The GAT1-mediated release of [(3)H]d-ASP was significantly enhanced in spinal cord gliosomes from the mouse model of ALS. This excessive [(3)H]d-...Continue Reading

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Citations

Aug 17, 2010·Cellular and Molecular Life Sciences : CMLS·Monica BariMauro Maccarrone
May 23, 2015·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Renaid B KimCassie S Mitchell
Dec 24, 2010·Journal of Neurochemistry·Marco MilaneseGiambattista Bonanno
Oct 26, 2013·Neuropharmacology·Uri Nimrod Ramírez-JarquínRicardo Tapia
Sep 16, 2016·Frontiers in Pharmacology·Anna Pittaluga
May 27, 2016·The Journal of Biological Chemistry·Tamami WakabayashiTomoko Kuwabara
Jan 11, 2020·Frontiers in Cellular Neuroscience·Soraya Wilke SalibaBernd L Fiebich
Nov 11, 2014·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration
Oct 14, 2014·Journal of Proteome Research·Karen E CarneyMark H G Verheijen

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