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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-85625-4 |
| _version_ | 1818845747278249984 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T05:34:34Z |
| format | Article |
| id | doaj.art-e57add55b48d470384d5902b47f71443 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T05:34:34Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e57add55b48d470384d5902b47f714432022-12-21T20:34:09ZengNature PortfolioScientific Reports2045-23222021-03-0111111110.1038/s41598-021-85625-4Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitroToru Murakawa-Hirachi0Yoshito Mizoguchi1Masahiro Ohgidani2Yoshinori Haraguchi3Akira Monji4Department of Psychiatry, Faculty of Medicine, Saga UniversityDepartment of Psychiatry, Faculty of Medicine, Saga UniversityDepartment of Psychiatry, Faculty of Medicine, Saga UniversityDepartment of Psychiatry, Faculty of Medicine, Saga UniversityDepartment of Psychiatry, Faculty of Medicine, Saga UniversityAbstract 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.https://doi.org/10.1038/s41598-021-85625-4 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-85625-4 |
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