{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:23:37Z","timestamp":1791404617338,"version":"4.3.3"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UGC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer\u2019s disease, Parkinson\u2019s disease, Amyotrophic lateral sclerosis and Huntington\u2019s 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.<\/jats:p>","DOI":"10.3390\/md20100645","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:58:51Z","timestamp":1666141131000},"page":"645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function"],"prefix":"10.3390","volume":"20","author":[{"given":"Swapna Kannothum","family":"Kandy","sequence":"first","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhura Milind","family":"Nimonkar","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suravi Sasmita","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupesh","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9783-2046","authenticated-orcid":false,"given":"Yogananda S.","family":"Markandeya","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","first-page":"1813","article-title":"Pictorial review of glutamate excitotoxicity: Fundamental concepts for neuroimaging","volume":"22","author":"Mark","year":"2001","journal-title":"AJNR Am. 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