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NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes

1
Program of Immunology, Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
2
Program of Immunology, Department of Pediatrics, CR-CHUS, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
*
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 400; https://doi.org/10.3390/cells8050400
Received: 10 April 2019 / Revised: 25 April 2019 / Accepted: 28 April 2019 / Published: 30 April 2019
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Abstract

Uptake of glutamate from the extracellular space and glutamate release to neurons are two major processes conducted by astrocytes in the central nervous system (CNS) that protect against glutamate excitotoxicity and strengthen neuronal firing, respectively. During inflammatory conditions in the CNS, astrocytes may lose one or both of these functions, resulting in accumulation of the extracellular glutamate, which eventually leads to excitotoxic neuronal death, which in turn worsens the CNS inflammation. NLRX1 is an innate immune NOD-like receptor that inhibits the major inflammatory pathways. It is localized in the mitochondria and was shown to inhibit cell death, enhance ATP production, and dampen oxidative stress. In the current work, using primary murine astrocyte cultures from WT and Nlrx1-/- mice, we demonstrate that NLRX1 potentiates astrocytic glutamate uptake by enhancing mitochondrial functions and the functional activity of glutamate transporters. Also, we report that NLRX1 inhibits glutamate release from astrocytes by repressing Ca2+-mediated glutamate exocytosis. Our study, for the first time, identified NLRX1 as a potential regulator of glutamate homeostasis in the CNS. View Full-Text
Keywords: NLRX1; astrocytes; CNS; glutamate uptake; glutamate release; excitotoxicity NLRX1; astrocytes; CNS; glutamate uptake; glutamate release; excitotoxicity
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Mahmoud, S.; Gharagozloo, M.; Simard, C.; Amrani, A.; Gris, D. NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes. Cells 2019, 8, 400.

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