Creatine protects against excitoxicity in an in vitro model of neurodegeneration.

Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing...

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Autores principales:	Just Genius, Johanna Geiger, Andreas Bender, Hans-Jürgen Möller, Thomas Klopstock, Dan Rujescu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/809674e423e84124b737ffd69afd54ed
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spelling	oai:doaj.org-article:809674e423e84124b737ffd69afd54ed2021-11-18T07:28:42ZCreatine protects against excitoxicity in an in vitro model of neurodegeneration.1932-620310.1371/journal.pone.0030554https://doaj.org/article/809674e423e84124b737ffd69afd54ed2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22347384/?tool=EBIhttps://doaj.org/toc/1932-6203Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H(2)O(2). In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H(2)O(2)-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity.Just GeniusJohanna GeigerAndreas BenderHans-Jürgen MöllerThomas KlopstockDan RujescuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e30554 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Just Genius Johanna Geiger Andreas Bender Hans-Jürgen Möller Thomas Klopstock Dan Rujescu Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
description	Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H(2)O(2). In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H(2)O(2)-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity.
format	article
author	Just Genius Johanna Geiger Andreas Bender Hans-Jürgen Möller Thomas Klopstock Dan Rujescu
author_facet	Just Genius Johanna Geiger Andreas Bender Hans-Jürgen Möller Thomas Klopstock Dan Rujescu
author_sort	Just Genius
title	Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
title_short	Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
title_full	Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
title_fullStr	Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
title_full_unstemmed	Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
title_sort	creatine protects against excitoxicity in an in vitro model of neurodegeneration.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/809674e423e84124b737ffd69afd54ed
work_keys_str_mv	AT justgenius creatineprotectsagainstexcitoxicityinaninvitromodelofneurodegeneration AT johannageiger creatineprotectsagainstexcitoxicityinaninvitromodelofneurodegeneration AT andreasbender creatineprotectsagainstexcitoxicityinaninvitromodelofneurodegeneration AT hansjurgenmoller creatineprotectsagainstexcitoxicityinaninvitromodelofneurodegeneration AT thomasklopstock creatineprotectsagainstexcitoxicityinaninvitromodelofneurodegeneration AT danrujescu creatineprotectsagainstexcitoxicityinaninvitromodelofneurodegeneration
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Creatine protects against excitoxicity in an in vitro model of neurodegeneration.

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