AUTHOR=Luo Su-mei , Li Long-yan , Guo Li-zhe , Wang Lu , Wang Yan-feng , Chen Na , Wang E. 

TITLE=Dexmedetomidine exerts an anti-inflammatory effect via α2 adrenoceptors to alleviate cognitive dysfunction in 5xFAD mice

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.978768

DOI=10.3389/fnagi.2022.978768

ISSN=1663-4365

ABSTRACT=<p><bold>Background:</bold> Inflammation promotes the progression of Alzheimer’s disease (AD). In this study, we explored the effect of dexmedetomidine on inflammation and cognitive function in a mouse model of AD.</p><p><bold>Methods:</bold> 5xFAD mice were intragastrically administered saline, dexmedetomidine, or dexmedetomidine and yohimbine for 14 days. The effects of dexmedetomidine on the acquisition and retention of memory in the Morris water-maze test and Y maze were evaluated. The deposition of amyloid beta protein (Abeta) and cytokine levels in the hippocampus were assessed. The expression of Bace1 protein and NFκB-p65 protein was assessed by Western blotting.</p><p><bold>Results:</bold> Compared with WT mice, 5xFAD mice exhibited cognitive impairment in the Morris water maze test and Y maze test. Cognitive decline was alleviated by dexmedetomidine and this was reversed by the α2 adrenoceptor antagonist yohimbine. Compared with saline treatment, dexmedetomidine led to a reduction in the Abeta deposition area (<italic>p</italic> &lt; 0.05) and in the mean gray value (<italic>p</italic> &lt; 0.01) in the hippocampus of 5xFAD mice. Compared with saline treatment, dexmedetomidine inhibited the activation of astrocytes and microglia in the hippocampal DG of 5xFAD mice and reduced the area of GFAP (<italic>p</italic> &lt; 0.01) and IBA1 (<italic>p</italic> &lt; 0.01). The level of IL-1β in the hippocampus decreased significantly after dexmedetomidine treatment compared with saline treatment in 5xFAD mice (<italic>p</italic> &lt; 0.01). Yohimbine neutralized the effects of dexmedetomidine. Dexmedetomidine inhibited the expression of BACE1 and NF-κB p65 (<italic>p</italic> &lt; 0.01), and these changes were reversed by yohimbine treatment.</p><p><bold>Conclusion:</bold> Dexmedetomidine alleviates cognitive decline, inhibits neuroinflammation, and prevents the deposition of Abeta in 5xFAD mice. The effect is mediated by the α2 adrenoceptor-mediated anti-inflammatory pathway. Dexmedetomidine may be effective for the treatment of AD and a better choice for the sedation of AD.</p>