Effects of electroacupuncture on cognitive function and neuronal autophagy in rats with D-galactose induced Alzheimer's disease / 针刺研究

ABSTRACT

OBJECTIVE: To observe the effect of electroacupuncture at "Baihui"(GV20) and "Shenshu"(BL23) on the expression of autophagy-related proteins in the hippocampus of rats with Alzheimer's disease (AD)，so as to explore its underlying mechanisms on improvement of AD. METHODS: Forty-eight male SD rats were randomly divided into blank control group, model group, electroacupuncture group and sham electroacupuncture group, with 12 rats in each group. The AD rat model was establish by intraperitoneal injection of D-galactose for 6 weeks. Rats in the electroacupuncture group received electroacupuncture (50 Hz, 1 mA)at GV20 and BL23 for 20 min each time after daily intraperitoneal injection. Rats in the sham electroacupuncture group received acupuncture at the local skin of GV20 and BL23 without electricity. After the intervention, Morris water maze and open field test were used to evaluate the learning and cognitive ability of rats in each group. The transmission electron microscope was used to observe the numerical density of synaptic in hippocampus, and the immunohistochemical staining was used to observe the paired helical filament protein-1 (PHF-1) in the hippocampus. Western blot was used to detected the expression of autophagy-related proteins phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), phosphorylated AKT (p-AKT), mammalian target of rapamycin (mTOR) in the hippocampus. RESULTS: Compared with the blank control group, the escape latency of the rats in the model group increased from day 2 to day 5 (P<0.01), and the ratio of the time through the quadrant of the original platform reduced （P<0.01）, in the open field test the distance of exercise, the number of uprights and the rate of exercise time in the central area decreased (P<0.01), meanwhile the density of hippocampus synapses decreased (P<0.01), the positive expression of PHF-1 and the relative expression of PI3K, AKT, p-AKT, and mTOR all increased (P<0.01). Compared with the model group, the escape latency of rats in the electroacupuncture group was shortened from day 2 to day 5 (P<0.01), and the ratio of the time through the quadrant of the original platform meanwhile, the distance of the open field test, the number of uprights, and the rate of central area exercise time up-regulated (P<0.01), the numerical density of hippocampus synatic increased (P<0.01), the positive expression of PHF-1 and the relative expression of PI3K, AKT, p-AKT, and mTOR all down-regulated (P<0.01). Compared with the model group, the expression of PI3K in the sham electroacupuncture group decreased (P<0.05). CONCLUSION: Electroacupuncture can improve learning and memory and cognitive impairment in AD rats, which may be associated with its effects in regulation of hippocampal autophagy and removal of neurofibrillary tangles by suppressing PI3K/AKT/mTOR signaling pathway.