Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD.
Sepsis-associated encephalopathy is a common neurological complication of sepsis. Despite advances in pathological and diagnostic investigations, its treatment remains a major challenge. In sepsis-associated encephalopathy, neuroinflammatory overactivation and mitochondrial damage are thought to contribute to cognitive and behavioral impairments. In this study, we found that administration of (−)-Epicatechin, a dietary flavonoid of the flavan-3-ol subgroup, improves memory deficits and behavior performance by ameliorating neuroinflammation, regulating mitochondria function, enhancing synaptic plasticity, and reducing neuronal loss in a mouse model of lipopolysaccharide-induced sepsis. We further show that the AMPK signaling pathway might be among the mechanisms involved in the beneficial memory effects. Our data demonstrated the potential of (−)-Epicatechin as a new drug candidate for the treatment of sepsis-associated cognitive impairment by targeting AMPK.
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