Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model most commonly used in research on the pathomechanisms of multiple sclerosis (MS). The inflammatory processes, glutamate excitotoxicity, and oxidative stress have been proposed as determinants accompanying demyelination and neuronal d...

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Autores principales:	Beata Dąbrowska-Bouta, Lidia Strużyńska, Marta Sidoryk-Węgrzynowicz, Grzegorz Sulkowski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	EAE glutamate receptor antagonist excitotoxicity oxidative stress -SH groups superoxide dismutase Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/24678a8eb71e4698bffcd77dd1ae88df
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spelling	oai:doaj.org-article:24678a8eb71e4698bffcd77dd1ae88df2021-11-11T16:48:48ZMemantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis10.3390/ijms2221113301422-00671661-6596https://doaj.org/article/24678a8eb71e4698bffcd77dd1ae88df2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11330https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Experimental autoimmune encephalomyelitis (EAE) is an animal model most commonly used in research on the pathomechanisms of multiple sclerosis (MS). The inflammatory processes, glutamate excitotoxicity, and oxidative stress have been proposed as determinants accompanying demyelination and neuronal degeneration during the course of MS/EAE. The aim of the current study was to characterize the role of NMDA receptors in the induction of oxidative stress during the course of EAE. The effect of memantine, the uncompetitive NMDA receptor antagonist, on modulation of neurological deficits and oxidative stress in EAE rats was analyzed using several experimental approaches. We demonstrated that the expression of antioxidative enzymes (superoxide dismutases SOD1 and SOD2) were elevated in EAE rat brains. Under the same experimental conditions, we observed alterations in oxidative stress markers such as increased levels of malondialdehyde (MDA) and decreased levels of sulfhydryl (-SH) groups, both protein and non-protein (indicating protein damage), and a decline in reduced glutathione. Importantly, pharmacological inhibition of ionotropic NMDA glutamate receptors by their antagonist memantine improved the physical activity of EAE rats, alleviated neurological deficits such as paralysis of tail and hind limbs, and modulated oxidative stress parameters (MDA, -SH groups, SOD’s). Furthermore, the current therapy aiming to suppress NMDAR-induced oxidative stress was partially effective when NMDAR’s antagonist was administered at an early (asymptomatic) stage of EAE.Beata Dąbrowska-BoutaLidia StrużyńskaMarta Sidoryk-WęgrzynowiczGrzegorz SulkowskiMDPI AGarticleEAEglutamate receptor antagonistexcitotoxicityoxidative stress-SH groupssuperoxide dismutaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11330, p 11330 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EAE glutamate receptor antagonist excitotoxicity oxidative stress -SH groups superoxide dismutase Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	EAE glutamate receptor antagonist excitotoxicity oxidative stress -SH groups superoxide dismutase Biology (General) QH301-705.5 Chemistry QD1-999 Beata Dąbrowska-Bouta Lidia Strużyńska Marta Sidoryk-Węgrzynowicz Grzegorz Sulkowski Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis
description	Experimental autoimmune encephalomyelitis (EAE) is an animal model most commonly used in research on the pathomechanisms of multiple sclerosis (MS). The inflammatory processes, glutamate excitotoxicity, and oxidative stress have been proposed as determinants accompanying demyelination and neuronal degeneration during the course of MS/EAE. The aim of the current study was to characterize the role of NMDA receptors in the induction of oxidative stress during the course of EAE. The effect of memantine, the uncompetitive NMDA receptor antagonist, on modulation of neurological deficits and oxidative stress in EAE rats was analyzed using several experimental approaches. We demonstrated that the expression of antioxidative enzymes (superoxide dismutases SOD1 and SOD2) were elevated in EAE rat brains. Under the same experimental conditions, we observed alterations in oxidative stress markers such as increased levels of malondialdehyde (MDA) and decreased levels of sulfhydryl (-SH) groups, both protein and non-protein (indicating protein damage), and a decline in reduced glutathione. Importantly, pharmacological inhibition of ionotropic NMDA glutamate receptors by their antagonist memantine improved the physical activity of EAE rats, alleviated neurological deficits such as paralysis of tail and hind limbs, and modulated oxidative stress parameters (MDA, -SH groups, SOD’s). Furthermore, the current therapy aiming to suppress NMDAR-induced oxidative stress was partially effective when NMDAR’s antagonist was administered at an early (asymptomatic) stage of EAE.
format	article
author	Beata Dąbrowska-Bouta Lidia Strużyńska Marta Sidoryk-Węgrzynowicz Grzegorz Sulkowski
author_facet	Beata Dąbrowska-Bouta Lidia Strużyńska Marta Sidoryk-Węgrzynowicz Grzegorz Sulkowski
author_sort	Beata Dąbrowska-Bouta
title	Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis
title_short	Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis
title_full	Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis
title_fullStr	Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis
title_full_unstemmed	Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis
title_sort	memantine modulates oxidative stress in the rat brain following experimental autoimmune encephalomyelitis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/24678a8eb71e4698bffcd77dd1ae88df
work_keys_str_mv	AT beatadabrowskabouta memantinemodulatesoxidativestressintheratbrainfollowingexperimentalautoimmuneencephalomyelitis AT lidiastruzynska memantinemodulatesoxidativestressintheratbrainfollowingexperimentalautoimmuneencephalomyelitis AT martasidorykwegrzynowicz memantinemodulatesoxidativestressintheratbrainfollowingexperimentalautoimmuneencephalomyelitis AT grzegorzsulkowski memantinemodulatesoxidativestressintheratbrainfollowingexperimentalautoimmuneencephalomyelitis
_version_	1718432227507830784

Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis

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