Persistent Overexposure to N-Methyl-D-Aspartate (NMDA) Calcium-Dependently Downregulates Glutamine Synthetase, Aquaporin 4, and Kir4.1 Channel in Mouse Cortical Astrocytes.

Neurotox Res. 2019 Jan;35(1):271-280. doi: 10.1007/s12640-018-9958-3. Epub 2018 Sep 15.

Skowrońska K1, Obara-Michlewska M1, Czarnecka A1, Dąbrowska K1, Zielińska M1, Albrecht J2.

Author information:

1     Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland.

2      Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland. Ten adres pocztowy jest chroniony przed spamowaniem. Aby go zobaczyć, konieczne jest włączenie w przeglądarce obsługi JavaScript..

Abstract

Astrocytes express N-methyl-D-aspartate (NMDA) receptor (NMDAR) but its functions in these cells are not well defined. This study shows that the sustained exposure (8-72 h) of mouse astrocytes to NMDA decreases the expression of the functional astroglia-specific proteins, glutamine synthetase (GS), and the water channel protein aquaporin-4 (AQP4) and also reduces GS activity. Similar to rat astrocytes (Obara-Michlewska et al. Neurochem Int 88:20-25, 2015), the exposure of mouse astrocytes to NMDA also decreased the expression of the inward rectifying potassium channel Kir4.1. NMDA failed to elicit the effects in those cells incubated in the absence of Ca2+ and in those in which the GluN1 subunit of the NMDAR was silenced with GluN1 siRNA. The downregulation of GS, AQP4, and Kir4.1 observed in vitro may reflect NMDAR-mediated alterations of astrocytic functions noted in central nervous system pathologies associated with increased glutamate (Glu) release and excitotoxic tissue damage.

KEYWORDS:

Aquaporin 4; Astrocytes; Excitotoxicity; GluN1; Glutamine synthetase; Kir4.1; NMDA receptor

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