NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes
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,...
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MDPI AG
2019-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/5/400 |
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| author | Shaimaa Mahmoud Marjan Gharagozloo Camille Simard Abdelaziz Amrani Denis Gris |
| author_facet | Shaimaa Mahmoud Marjan Gharagozloo Camille Simard Abdelaziz Amrani Denis Gris |
| author_sort | Shaimaa Mahmoud |
| collection | DOAJ |
| description | 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 <i>Nlrx1<sup>-/-</sup></i> 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 Ca<sup>2+</sup>-mediated glutamate exocytosis. Our study, for the first time, identified NLRX1 as a potential regulator of glutamate homeostasis in the CNS. |
| first_indexed | 2024-03-12T04:31:46Z |
| format | Article |
| id | doaj.art-5e71562c83bb4d299676ed1c8b0a518e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T04:31:46Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5e71562c83bb4d299676ed1c8b0a518e2023-09-03T10:03:42ZengMDPI AGCells2073-44092019-04-018540010.3390/cells8050400cells8050400NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by AstrocytesShaimaa Mahmoud0Marjan Gharagozloo1Camille Simard2Abdelaziz Amrani3Denis Gris4Program of Immunology, Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaProgram of Immunology, Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaProgram of Immunology, Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaProgram of Immunology, Department of Pediatrics, CR-CHUS, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaProgram of Immunology, Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaUptake 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 <i>Nlrx1<sup>-/-</sup></i> 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 Ca<sup>2+</sup>-mediated glutamate exocytosis. Our study, for the first time, identified NLRX1 as a potential regulator of glutamate homeostasis in the CNS.https://www.mdpi.com/2073-4409/8/5/400NLRX1astrocytesCNSglutamate uptakeglutamate releaseexcitotoxicity |
| spellingShingle | Shaimaa Mahmoud Marjan Gharagozloo Camille Simard Abdelaziz Amrani Denis Gris NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes Cells NLRX1 astrocytes CNS glutamate uptake glutamate release excitotoxicity |
| title | NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes |
| title_full | NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes |
| title_fullStr | NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes |
| title_full_unstemmed | NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes |
| title_short | NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes |
| title_sort | nlrx1 enhances glutamate uptake and inhibits glutamate release by astrocytes |
| topic | NLRX1 astrocytes CNS glutamate uptake glutamate release excitotoxicity |
| url | https://www.mdpi.com/2073-4409/8/5/400 |
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