Electroacupuncture improves synaptic plasticity and cognitive dysfunction via down-regulating HDAC3 in mice of Alzheimer’s disease

To observe the effect of electroacupuncture (EA) on histone deacetylase 3 (HDAC3), synaptic plasticity and N-methyl-D-aspartate (NMDA) receptors in the hippocampus of mice with Alzheimer's disease (AD), so as to explore the underlying mechanism of EA in treatment of AD.

5XFAD mice were randomly divided into EA group, model group and sham-acupuncture group, with 13 mice in both the EA group and the model group, and 7 mice in the sham-acupuncture group. Thirteen wild-type mice from the same litter were taken as the normal control group. The mice in the EA group received EA at "Baihui" (GV20) and "Dazhui" (GV14) for 15 min once daily, 6 times a week for 4 weeks. The mice in the sham-acupuncture group received sham EA, i. e., the needle was inserted into the rubber clay which was placed on the surface of the corresponding acupoints. The novel object recognition (NOR), Y-maze and Morris water maze (MWM) tests were used to observe the cognitive functions of mice. Electrophysiological technique was used to detect long-term potentiation (LTP) of the hippocampal neurons and Western blot was used to detect the relative expressions of HDAC3 and NMDAR-related receptors (NMDAR1, NMDAR2A, NMDAR2B) in the hippocampus.

Compared with the normal control group, 5XFAD mice in the model group showed decreased (P<0.01, P<0.05) preference index for new object recognition, alternative arm ratio (AAR), number of times crossing the original platform, percentage of time and distance traveled in the target quadrant, NMDAR2B, NMDAR2A and NMDAR1 protein expression levels, with prolonged (P<0.01) escape latency, and increased (P<0.05) protein relative expression of HDAC3. At the same time, with high-frequency stimulation, the slope of fEPSP was decreased (P<0.01, P<0.05) in the 5XFAD mice. After EA intervention, comparison between the EA and the model groups revealed that, the preference index for new object recognition, AAR were increased (P<0.01, P<0.05) in the EA group, the escape latency was shortened (P<0.05), and the number of times crossing the platform, percentage of time and distance traveled in the target quadrant, the slope of fEPSP, and the protein relative expressions of NMDAR2B, NMDAR2A and NMDAR1 in the hippocampus were increased (P<0.01, P<0.05), while the protein relative expression of HDAC3 decreased (P<0.01). Compared with sham-acupuncture group, the above indexes improved to different degree in the EA group (P<0.01, P<0.05).

EA of GV20 and GV14 can restore the impaired LTP and improve the cognitive impairment, which may be related to increasing the expressions of NMDA-related receptor proteins and down-regulating the expression of HDAC3 in the hippocampus of 5XFAD mice.