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Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model
PURPOSE: Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which is characterized by memory loss and cognitive deficits. The neuroprotective role of milrinone on the injury of spinal cord or cerebral ischemia-reperfusion has been confirmed. However, the accurate function of milrinone...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256386/ https://www.ncbi.nlm.nih.gov/pubmed/34234439 http://dx.doi.org/10.2147/NDT.S312648 |
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author | Chen, Qingyou Yin, Yue Li, Li Zhang, Yanjiao He, Wei Shi, Yan |
author_facet | Chen, Qingyou Yin, Yue Li, Li Zhang, Yanjiao He, Wei Shi, Yan |
author_sort | Chen, Qingyou |
collection | PubMed |
description | PURPOSE: Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which is characterized by memory loss and cognitive deficits. The neuroprotective role of milrinone on the injury of spinal cord or cerebral ischemia-reperfusion has been confirmed. However, the accurate function of milrinone on AD pathogeny is still unclear. METHODS: APP/PS1 transgenic mouse was used to explore the role of milrinone in behaviour tests, and the effects on histopathologic features of AD such as the formation of neuronal amyloid-β (Aβ) plaque, microglial activation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Lipopolysaccharide (LPS)/Aβ-treated BV-2 cells were used to understand the anti-inflammation mechanism of milrinone on AD in vitro. RESULTS: Our in vivo results showed that milrinone ameliorates the memory functions of AD mice. Meanwhile, milrinone reduced Aβ deposits, repressed microglial activation and tau protein hyperphosphorylation, attenuated the oxidative stress, and decreased the levels of inflammatory cytokines. The in vitro results demonstrated that milrinone could inhibit the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α via regulation of NLRP3 inflammasomes and TLR4/MyD88/NF-κB signalling pathway. CONCLUSION: Overall, milrinone could ameliorate the memory loss and cognitive deficits through repressing the multiple pathological processes of AD, suggesting that milrinone may be an underlying and effective drug for treating AD clinically. |
format | Online Article Text |
id | pubmed-8256386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-82563862021-07-06 Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model Chen, Qingyou Yin, Yue Li, Li Zhang, Yanjiao He, Wei Shi, Yan Neuropsychiatr Dis Treat Original Research PURPOSE: Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which is characterized by memory loss and cognitive deficits. The neuroprotective role of milrinone on the injury of spinal cord or cerebral ischemia-reperfusion has been confirmed. However, the accurate function of milrinone on AD pathogeny is still unclear. METHODS: APP/PS1 transgenic mouse was used to explore the role of milrinone in behaviour tests, and the effects on histopathologic features of AD such as the formation of neuronal amyloid-β (Aβ) plaque, microglial activation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Lipopolysaccharide (LPS)/Aβ-treated BV-2 cells were used to understand the anti-inflammation mechanism of milrinone on AD in vitro. RESULTS: Our in vivo results showed that milrinone ameliorates the memory functions of AD mice. Meanwhile, milrinone reduced Aβ deposits, repressed microglial activation and tau protein hyperphosphorylation, attenuated the oxidative stress, and decreased the levels of inflammatory cytokines. The in vitro results demonstrated that milrinone could inhibit the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α via regulation of NLRP3 inflammasomes and TLR4/MyD88/NF-κB signalling pathway. CONCLUSION: Overall, milrinone could ameliorate the memory loss and cognitive deficits through repressing the multiple pathological processes of AD, suggesting that milrinone may be an underlying and effective drug for treating AD clinically. Dove 2021-06-30 /pmc/articles/PMC8256386/ /pubmed/34234439 http://dx.doi.org/10.2147/NDT.S312648 Text en © 2021 Chen et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Chen, Qingyou Yin, Yue Li, Li Zhang, Yanjiao He, Wei Shi, Yan Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model |
title | Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model |
title_full | Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model |
title_fullStr | Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model |
title_full_unstemmed | Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model |
title_short | Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model |
title_sort | milrinone ameliorates the neuroinflammation and memory function of alzheimer’s disease in an app/ps1 mouse model |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256386/ https://www.ncbi.nlm.nih.gov/pubmed/34234439 http://dx.doi.org/10.2147/NDT.S312648 |
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