Acupuncture has been shown to ameliorate cognitive impairment of Alzheimer's disease. Acupoints and stimulation frequency influence the therapeutic effect of electroacupuncture. Rat models of Alzheimer's disease were established by injecting amyloid beta 1-42 (Aβ1-42) into the bilateral lateral ventricles. Electroacupuncture at 2, 30, and 50 Hz was carried out at Baihui (GV20; 15° obliquely to a depth of 2 mm) and Shenshu (BL23; perpendicularly to 4-6 mm depth), once a day for 20 minutes (each), for 15 days, taking a break every 7 days. The Morris water maze test was conducted to assess the learning and memory. The expression levels of glycogen synthase kinase-3β (GSK-3β), pSer9-GSK-3β, pTyr216-GSK-3β, amyloid precursor protein and Aβ1-40 in the hippocampus were determined by western blot assay. Results demonstrated that electroacupuncture treatment at different frequencies markedly improved learning and memory ability, increased synaptic curvatures, decreased the width of synaptic clefts, thickened postsynaptic densities, and downregulated the expression of GSK-3β, amyloid precursor protein, and Aβ1-40. pSer9-GSK-3β expression markedly decreased, while pTyr216-GSK-3β expression increased. High-frequency (50 Hz) electroacupuncture was more effective than low (2 Hz) or medium-frequency (30 Hz) electroacupuncture. In conclusion, electroacupuncture treatment exerts a protective effect against Aβ1-42-induced learning and memory deficits and synapse-ultrastructure impairment via inhibition of GSK-3β activity. Moreover, high-frequency electroacupuncture was the most effective therapy.
Keywords: Alzheimer's disease; Baihui (GV20); Shenshu (BL23); cognitive impairment; different frequencies; electroacupuncture; glycogen synthase kinase-3β; hippocampus; nerve regeneration; neural regeneration; postsynaptic density; synaptic curvatures; width of synaptic cleft.