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DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation

Our previous study has demonstrated that chronic stress could cause cognitive deficits and tau pathology. However, the underlying mechanism and whether/how DI-3-n-Butylphthalide (NBP) ameliorates these effects are still unclear. Here, Wild-type mice were subjected to chronic unpredictable and mild s...

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Autores principales: Chen, Xiu, He, Juan-Ling, Liu, Xue-Ting, Zhao, Na, Geng, Fan, Zhu, Meng-Meng, Liu, Gong-Ping, Ren, Qing-Guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489537/
https://www.ncbi.nlm.nih.gov/pubmed/36160816
http://dx.doi.org/10.1016/j.ynstr.2022.100486
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author Chen, Xiu
He, Juan-Ling
Liu, Xue-Ting
Zhao, Na
Geng, Fan
Zhu, Meng-Meng
Liu, Gong-Ping
Ren, Qing-Guo
author_facet Chen, Xiu
He, Juan-Ling
Liu, Xue-Ting
Zhao, Na
Geng, Fan
Zhu, Meng-Meng
Liu, Gong-Ping
Ren, Qing-Guo
author_sort Chen, Xiu
collection PubMed
description Our previous study has demonstrated that chronic stress could cause cognitive deficits and tau pathology. However, the underlying mechanism and whether/how DI-3-n-Butylphthalide (NBP) ameliorates these effects are still unclear. Here, Wild-type mice were subjected to chronic unpredictable and mild stress (CUMS) for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resilient) groups based on behavioral tests. Then, NBP (30 mg/kg i.g) was administered for 4 weeks. Morris water maze (MWM), Western-blot, Golgi staining, immunofluorescence staining and ELISA were used to examine behavioral, biochemical, and pathological changes. The results showed that both depressive and resilient mice displayed spatial memory deficits and an accumulation of tau in the hippocampus. Activated microglia and NLRP3 inflammasome were found after 8-week chronic stress. We also found a decreased level of postsynaptic density (PSD) related proteins (PSD93 and PSD95) and decreased the number of dendritic spines in the hippocampus. Interestingly, almost all the pathological changes in depressive and resilient mice previously mentioned could be reversed by NBP treatment. To further investigate the role of NLRP3 inflammasome in chronic stress-induced cognitive deficits, NLRP3 KO mice were also exposed to chronic stress. And these changes induced by chronic stress could not be found in NLRP3 KO mice. These results show an important role for the NLRP3/caspase-1/IL-1β axis in chronic stress-induced cognitive deficits and NBP meliorates cognitive impairments and selectively attenuates phosphorylated tau accumulation in stressed mice through regulation of NLRP3 inflammatory signaling pathway.
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spelling pubmed-94895372022-09-22 DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation Chen, Xiu He, Juan-Ling Liu, Xue-Ting Zhao, Na Geng, Fan Zhu, Meng-Meng Liu, Gong-Ping Ren, Qing-Guo Neurobiol Stress Original Research Article Our previous study has demonstrated that chronic stress could cause cognitive deficits and tau pathology. However, the underlying mechanism and whether/how DI-3-n-Butylphthalide (NBP) ameliorates these effects are still unclear. Here, Wild-type mice were subjected to chronic unpredictable and mild stress (CUMS) for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resilient) groups based on behavioral tests. Then, NBP (30 mg/kg i.g) was administered for 4 weeks. Morris water maze (MWM), Western-blot, Golgi staining, immunofluorescence staining and ELISA were used to examine behavioral, biochemical, and pathological changes. The results showed that both depressive and resilient mice displayed spatial memory deficits and an accumulation of tau in the hippocampus. Activated microglia and NLRP3 inflammasome were found after 8-week chronic stress. We also found a decreased level of postsynaptic density (PSD) related proteins (PSD93 and PSD95) and decreased the number of dendritic spines in the hippocampus. Interestingly, almost all the pathological changes in depressive and resilient mice previously mentioned could be reversed by NBP treatment. To further investigate the role of NLRP3 inflammasome in chronic stress-induced cognitive deficits, NLRP3 KO mice were also exposed to chronic stress. And these changes induced by chronic stress could not be found in NLRP3 KO mice. These results show an important role for the NLRP3/caspase-1/IL-1β axis in chronic stress-induced cognitive deficits and NBP meliorates cognitive impairments and selectively attenuates phosphorylated tau accumulation in stressed mice through regulation of NLRP3 inflammatory signaling pathway. Elsevier 2022-09-13 /pmc/articles/PMC9489537/ /pubmed/36160816 http://dx.doi.org/10.1016/j.ynstr.2022.100486 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Chen, Xiu
He, Juan-Ling
Liu, Xue-Ting
Zhao, Na
Geng, Fan
Zhu, Meng-Meng
Liu, Gong-Ping
Ren, Qing-Guo
DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation
title DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation
title_full DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation
title_fullStr DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation
title_full_unstemmed DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation
title_short DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation
title_sort di-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of nlrp3-mediated neuroinflammation
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489537/
https://www.ncbi.nlm.nih.gov/pubmed/36160816
http://dx.doi.org/10.1016/j.ynstr.2022.100486
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