Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders
Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake...
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MDPI AG
2022-03-01
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| author | Sairaj Satarker Sree Lalitha Bojja Prasada Chowdari Gurram Jayesh Mudgal Devinder Arora Madhavan Nampoothiri |
| author_facet | Sairaj Satarker Sree Lalitha Bojja Prasada Chowdari Gurram Jayesh Mudgal Devinder Arora Madhavan Nampoothiri |
| author_sort | Sairaj Satarker |
| collection | DOAJ |
| description | Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake mechanisms. Astrocytes modulate calcium-mediated excitability and release several neurotransmitters and neuromodulators, including glutamate, and significantly modulate neurotransmission. Accumulating evidence supports the concept of excitotoxicity caused by astrocytic glutamatergic release in pathological conditions. Thus, the current review highlights different vesicular and non-vesicular mechanisms of astrocytic glutamate release and their implication in neurodegenerative diseases. As in presynaptic neurons, the vesicular release of astrocytic glutamate is also primarily meditated by calcium-mediated exocytosis. V-ATPase is crucial in the acidification and maintenance of the gradient that facilitates the vesicular storage of glutamate. Along with these, several other components, such as cystine/glutamate antiporter, hemichannels, BEST-1, TREK-1, purinergic receptors and so forth, also contribute to glutamate release under physiological and pathological conditions. Events of hampered glutamate uptake could promote inflamed astrocytes to trigger repetitive release of glutamate. This could be favorable towards the development and worsening of neurodegenerative diseases. Therefore, across neurodegenerative diseases, we review the relations between defective glutamatergic signaling and astrocytic vesicular and non-vesicular events in glutamate homeostasis. The optimum regulation of astrocytic glutamatergic transmission could pave the way for the management of these diseases and add to their therapeutic value. |
| first_indexed | 2024-03-09T12:00:30Z |
| format | Article |
| id | doaj.art-4fd348ec5ba146609e47ed924f69b632 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:00:30Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4fd348ec5ba146609e47ed924f69b6322023-11-30T23:04:01ZengMDPI AGCells2073-44092022-03-01117113910.3390/cells11071139Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative DisordersSairaj Satarker0Sree Lalitha Bojja1Prasada Chowdari Gurram2Jayesh Mudgal3Devinder Arora4Madhavan Nampoothiri5Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaSeveral neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake mechanisms. Astrocytes modulate calcium-mediated excitability and release several neurotransmitters and neuromodulators, including glutamate, and significantly modulate neurotransmission. Accumulating evidence supports the concept of excitotoxicity caused by astrocytic glutamatergic release in pathological conditions. Thus, the current review highlights different vesicular and non-vesicular mechanisms of astrocytic glutamate release and their implication in neurodegenerative diseases. As in presynaptic neurons, the vesicular release of astrocytic glutamate is also primarily meditated by calcium-mediated exocytosis. V-ATPase is crucial in the acidification and maintenance of the gradient that facilitates the vesicular storage of glutamate. Along with these, several other components, such as cystine/glutamate antiporter, hemichannels, BEST-1, TREK-1, purinergic receptors and so forth, also contribute to glutamate release under physiological and pathological conditions. Events of hampered glutamate uptake could promote inflamed astrocytes to trigger repetitive release of glutamate. This could be favorable towards the development and worsening of neurodegenerative diseases. Therefore, across neurodegenerative diseases, we review the relations between defective glutamatergic signaling and astrocytic vesicular and non-vesicular events in glutamate homeostasis. The optimum regulation of astrocytic glutamatergic transmission could pave the way for the management of these diseases and add to their therapeutic value.https://www.mdpi.com/2073-4409/11/7/1139astrocyteglutamateneurodegenerative diseasesV-ATPasescalciumexocytosis |
| spellingShingle | Sairaj Satarker Sree Lalitha Bojja Prasada Chowdari Gurram Jayesh Mudgal Devinder Arora Madhavan Nampoothiri Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders Cells astrocyte glutamate neurodegenerative diseases V-ATPases calcium exocytosis |
| title | Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders |
| title_full | Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders |
| title_fullStr | Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders |
| title_full_unstemmed | Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders |
| title_short | Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders |
| title_sort | astrocytic glutamatergic transmission and its implications in neurodegenerative disorders |
| topic | astrocyte glutamate neurodegenerative diseases V-ATPases calcium exocytosis |
| url | https://www.mdpi.com/2073-4409/11/7/1139 |
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