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Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function

Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate recepto...

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Autores principales: Kandy, Swapna Kannothum, Nimonkar, Madhura Milind, Dash, Suravi Sasmita, Mehta, Bhupesh, Markandeya, Yogananda S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605357/
https://www.ncbi.nlm.nih.gov/pubmed/36286468
http://dx.doi.org/10.3390/md20100645
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author Kandy, Swapna Kannothum
Nimonkar, Madhura Milind
Dash, Suravi Sasmita
Mehta, Bhupesh
Markandeya, Yogananda S.
author_facet Kandy, Swapna Kannothum
Nimonkar, Madhura Milind
Dash, Suravi Sasmita
Mehta, Bhupesh
Markandeya, Yogananda S.
author_sort Kandy, Swapna Kannothum
collection PubMed
description Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate receptors, calcium overload, mitochondrial dysfunction and excessive reactive oxygen species (ROS) formation are a few of the suggested key mechanisms. Astaxanthin (AST), a carotenoid, is known to act as an antioxidant and protect neurons from excitotoxic injuries. However, the exact molecular mechanism of AST neuroprotection is not clear. Thus, in this study, we investigated the role of AST in neuroprotection in excitotoxicity. We utilized primary cortical neuronal culture and live cell fluorescence imaging for the study. Our results suggest that AST prevents neuronal death, reduces ROS formation and decreases the abnormal mitochondrial membrane depolarization induced by excitotoxic glutamate insult. Additionally, AST modulates intracellular calcium levels by inhibiting peak and irreversible secondary sustained calcium levels in neurons. Furthermore, AST regulates the ionotropic glutamate subtype receptors NMDA, AMPA, KA and mitochondrial calcium. Moreover, AST decreases NMDA and AMPA receptor protein expression levels, while KA remains unaffected. Overall, our results indicate that AST protects neurons from excitotoxic neuronal injury by regulating ionotropic glutamate receptors, cytosolic secondary calcium rise and mitochondrial calcium buffering. Hence, AST could be a promising therapeutic agent against excitotoxic insults in neurodegenerative diseases.
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spelling pubmed-96053572022-10-27 Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function Kandy, Swapna Kannothum Nimonkar, Madhura Milind Dash, Suravi Sasmita Mehta, Bhupesh Markandeya, Yogananda S. Mar Drugs Article Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate receptors, calcium overload, mitochondrial dysfunction and excessive reactive oxygen species (ROS) formation are a few of the suggested key mechanisms. Astaxanthin (AST), a carotenoid, is known to act as an antioxidant and protect neurons from excitotoxic injuries. However, the exact molecular mechanism of AST neuroprotection is not clear. Thus, in this study, we investigated the role of AST in neuroprotection in excitotoxicity. We utilized primary cortical neuronal culture and live cell fluorescence imaging for the study. Our results suggest that AST prevents neuronal death, reduces ROS formation and decreases the abnormal mitochondrial membrane depolarization induced by excitotoxic glutamate insult. Additionally, AST modulates intracellular calcium levels by inhibiting peak and irreversible secondary sustained calcium levels in neurons. Furthermore, AST regulates the ionotropic glutamate subtype receptors NMDA, AMPA, KA and mitochondrial calcium. Moreover, AST decreases NMDA and AMPA receptor protein expression levels, while KA remains unaffected. Overall, our results indicate that AST protects neurons from excitotoxic neuronal injury by regulating ionotropic glutamate receptors, cytosolic secondary calcium rise and mitochondrial calcium buffering. Hence, AST could be a promising therapeutic agent against excitotoxic insults in neurodegenerative diseases. MDPI 2022-10-18 /pmc/articles/PMC9605357/ /pubmed/36286468 http://dx.doi.org/10.3390/md20100645 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kandy, Swapna Kannothum
Nimonkar, Madhura Milind
Dash, Suravi Sasmita
Mehta, Bhupesh
Markandeya, Yogananda S.
Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
title Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
title_full Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
title_fullStr Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
title_full_unstemmed Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
title_short Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
title_sort astaxanthin protection against neuronal excitotoxicity via glutamate receptor inhibition and improvement of mitochondrial function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605357/
https://www.ncbi.nlm.nih.gov/pubmed/36286468
http://dx.doi.org/10.3390/md20100645
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