کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7279483 1473897 2018 45 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice
چکیده انگلیسی
Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, and neuronal loss, accompanied by neuroinflammation. Neuroinflammatory processes are thought to contribute to AD pathophysiology. Metformin has been reported to have anti-inflammatory efficacy. However, whether metformin is responsible for the anti-neuroinflammation and neuroprotection on APPswe/PS1ΔE9 (APP/PS1) mice remains unclear. Here we showed that metformin attenuated spatial memory deficit, neuron loss in the hippocampus and enhanced neurogenesis in APP/PS1 mice. In addition, metformin administration decreased amyloid-β (Aβ) plaque load and chronic inflammation (activated microglia and astrocytes as well as pro-inflammatory mediators) in the hippocampus and cortex. Further study demonstrated that treatment with metformin enhanced cerebral AMPK activation. Meanwhile, metformin notably suppressed the activation of P65 NF-κB, mTOR and S6K, reduced Bace1 protein expression. Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PS1 mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NF-κB signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 69, March 2018, Pages 351-363
نویسندگان
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