Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice
Abstract
Alzheimer'sdisease(AD) is characterized by deposition of amyloid-β (Aβ)plaques, neurofibrillary tangles, andneuronal loss, accompaniedbyneuroinflammation. Neuroinflammatoryprocesses are thought to contribute toAD pathophysiology. Metformin has been reported to have anti-inflammatory efficacy. However, whether metformin is responsible for the anti-neuroinflammationand 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.
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