Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro

Abstract The pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and a...

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Autores principales:	Toru Murakawa-Hirachi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshinori Haraguchi, Akira Monji
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e57add55b48d470384d5902b47f71443
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spelling	oai:doaj.org-article:e57add55b48d470384d5902b47f714432021-12-02T11:39:33ZEffect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro10.1038/s41598-021-85625-42045-2322https://doaj.org/article/e57add55b48d470384d5902b47f714432021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85625-4https://doaj.org/toc/2045-2322Abstract The pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation of microglial cells in animal models of AD. However, it remains to be tested whether memantine can directly affect microglial cell function. In this study, we examined whether pretreatment with memantine affects intracellular NO and Ca2+ mobilization using DAF-2 and Fura-2 imaging, respectively, and tested the effects of memantine on phagocytic activity by human β-Amyloid (1–42) phagocytosis assay in rodent microglial cells. Pretreatment with memantine did not affect production of NO or intracellular Ca2+ elevation induced by TNF in rodent microglial cells. Pretreatment with memantine also did not affect the mRNA expression of pro-inflammatory (TNF, IL-1β, IL-6 and CD45) or anti-inflammatory (IL-10, TGF-β and arginase) phenotypes in rodent microglial cells. In addition, pretreatment with memantine did not affect the amount of human β-Amyloid (1–42) phagocytosed by rodent microglial cells. Moreover, we observed that pretreatment with memantine did not affect 11 major proteins, which mainly function in the phagocytosis and degradation of β-Amyloid (1–42), including TREM2, DAP12 and neprilysin in rodent microglial cells. To the best of our knowledge, this is the first report to suggest that memantine does not directly modulate intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells. Considering the neuroinflammation hypothesis of AD, the results might be important to understand the effect of memantine in the brain.Toru Murakawa-HirachiYoshito MizoguchiMasahiro OhgidaniYoshinori HaraguchiAkira MonjiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Toru Murakawa-Hirachi Yoshito Mizoguchi Masahiro Ohgidani Yoshinori Haraguchi Akira Monji Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro
description	Abstract The pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation of microglial cells in animal models of AD. However, it remains to be tested whether memantine can directly affect microglial cell function. In this study, we examined whether pretreatment with memantine affects intracellular NO and Ca2+ mobilization using DAF-2 and Fura-2 imaging, respectively, and tested the effects of memantine on phagocytic activity by human β-Amyloid (1–42) phagocytosis assay in rodent microglial cells. Pretreatment with memantine did not affect production of NO or intracellular Ca2+ elevation induced by TNF in rodent microglial cells. Pretreatment with memantine also did not affect the mRNA expression of pro-inflammatory (TNF, IL-1β, IL-6 and CD45) or anti-inflammatory (IL-10, TGF-β and arginase) phenotypes in rodent microglial cells. In addition, pretreatment with memantine did not affect the amount of human β-Amyloid (1–42) phagocytosed by rodent microglial cells. Moreover, we observed that pretreatment with memantine did not affect 11 major proteins, which mainly function in the phagocytosis and degradation of β-Amyloid (1–42), including TREM2, DAP12 and neprilysin in rodent microglial cells. To the best of our knowledge, this is the first report to suggest that memantine does not directly modulate intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells. Considering the neuroinflammation hypothesis of AD, the results might be important to understand the effect of memantine in the brain.
format	article
author	Toru Murakawa-Hirachi Yoshito Mizoguchi Masahiro Ohgidani Yoshinori Haraguchi Akira Monji
author_facet	Toru Murakawa-Hirachi Yoshito Mizoguchi Masahiro Ohgidani Yoshinori Haraguchi Akira Monji
author_sort	Toru Murakawa-Hirachi
title	Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro
title_short	Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro
title_full	Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro
title_fullStr	Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro
title_full_unstemmed	Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro
title_sort	effect of memantine, an anti-alzheimer’s drug, on rodent microglial cells in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e57add55b48d470384d5902b47f71443
work_keys_str_mv	AT torumurakawahirachi effectofmemantineanantialzheimersdrugonrodentmicroglialcellsinvitro AT yoshitomizoguchi effectofmemantineanantialzheimersdrugonrodentmicroglialcellsinvitro AT masahiroohgidani effectofmemantineanantialzheimersdrugonrodentmicroglialcellsinvitro AT yoshinoriharaguchi effectofmemantineanantialzheimersdrugonrodentmicroglialcellsinvitro AT akiramonji effectofmemantineanantialzheimersdrugonrodentmicroglialcellsinvitro
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Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro

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