Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 69, Issue -, Pages 351-363Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2017.12.009
Keywords
Metformin; Alzheimer disease; Neuroinflammation; Neurogenesis; AMPK; mTOR; NF-kappa B
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Funding
- National Natural Science Foundation of China [81371217, 81470205, 81501014]
- National Funds of Developing Local Colleges and Universities [B16056001]
- Natural Science Foundation of Guangdong [2017A030313520]
- Outstanding Young People Project of Guangdong Province [Yq2013137]
- Science and Technology Foundation of Guangdong Province [2016A020214019]
- Science and Technology Foundation of Guangzhou [201707010231]
- Science Foundation of Education Bureau of Guangzhou City [1201610239]
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Alzheimer's disease (AD) is characterized by deposition of amyloid-beta (A beta) 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/PS1 Delta E9 (APP/PS1) mice remains unclear. Here we showed that metformin attenuated spatial memory deficit, neuron loss in the hippocampus and enhanced neurogenesis in APP/PSI mice. In addition, metformin administration decreased amyloid-beta (A beta) 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-kappa B, mTOR and S6K, reduced Bace1 protein expression. Our data suggest that metformin can exert functional recovery of memory deficits and neuroprotective effect on APP/PSI mice via triggering neurogenesis and anti-inflammation mediated by regulating AMPK/mTOR/S6K/Bace1 and AMPK/P65 NE-kappa B signaling pathways in the hippocampus, which may contribute to improvement in neurological deficits. (C) 2017 Elsevier Inc. All rights reserved.
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