Abstract
Objective:Studies have shown that electroacupuncture(EA)can alleviate cognitive impairments from Alzheimer's disease(AD)by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK),but the specific mechanism involved remains to be elucidated.Therefore,this study explores the potential mechanism by which EA improves cognitive function from the perspective of mito-chondrial dynamics.Methods:The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKα1-subunit conditional knockout(AMPKα1-cKO)were used for experiments.To evaluate the effects of EA treatment on cognitive function,the T-maze and Morris water maze were used.In addition,chemical exchange saturation transfer,thioflavin staining,transmission electron microscopy,mitochon-drial membrane potential,and Western blotting were used to examine the potential mechanisms under-lying the effects of EA on APP/PS1 mice.Results:Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment.Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1 α)pathway increased pathological amyloid-β(Aβ)deposition and aggravated the dysfunction in mitochondrial dynamics.In addition,EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway,specifically by reducing pathological Aβ deposition,normalizing energy metabolism,protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins,and downregulating the expression of fission pro-teins.However,the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout.Conclusion:The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.
万方数据