Electroacupuncture improves learning-memory ability possibly by suppressing apoptosis and down-regulating expression of apoptosis-related proteins in hippocampus and cerebral cortex in immature mice with Alzheimer's disease

Abstract

To investigate the effect of electroacupuncture (EA) at "Baihui"(GV20), "Fengfu"(GV16) and bilateral "Shenshu"(BL23) on learning-memory ability, apoptosis in the hippocampus and expression of Aβ, Caspase 3, Bax and Bcl-2 proteins in the hippocampus and cerebral cortex in immature mice with Alzheimer's disease (AD), so as to explore its mechanism underlying improvement of AD. Forty APP/PS1 transgenic male young mice were equally randomized into model and EA groups and 20 C57BL/6J male young mice were used as the normal control. EA (10 Hz, about 2 mA) was applied to GV20-BL23 and GV16-BL23 for 20 min, once daily, 6 days a week for 16 weeks. The Morris water maze swimming test was used to evaluate the animals' learning-memory ability. Congo red staining and immunohistochemical staining were used to detect senile plaques in the hippocampus (dentate gyrus) and cerebral cortex tissues. Terminal deoxynucleotidyl transferase-mediated dUTP Nick-end Labeling (TUNEL) was used to detect the cellular apoptosis of hippocampus. The expression levels of apoptosis related factors Caspase 3, Bax and Bcl-2 were detected by Western blot. After modeling, the escape latency of place navigation test of Morris water maze swimming tasks was significantly increased (P<0.05), while the number of platform crossing and residence time in the platform quadrant of spatial exploration test were significantly decreased in the model group in contrast to the normal control group (P<0.05). The number of apoptotic cells in the hippocampus and expression levels of Aβ, Caspase 3 and Bax proteins in the hippocampus and cerebral cortex were significantly up-regulated in the model group relevant to the normal control group (P<0.05). Following EA intervention, the escape latency of place navigation test of Morris water maze swimming tasks was significantly decreased (P<0.05), while the number of platform crossing and residence time in the platform quadrant of spatial exploration test were significantly increased in the EA group in contrast to the model group (P<0.05). The hippocampal apoptotic cells, the expression of Aβ, Caspase 3 and Bax proteins in hippocampus and cerebral cortex were evidently down-regulated in the EA group in contrast to the model group (P<0.05). Whereas the ratio of Bcl-2/Bax was significantly decreased in the model group relevant to the normal control group (P<0.05) and considerably increased in the EA group in contrast to the model group (P<0.05). No significant changes were found in the expression levels of Bcl-2 after modeling and after EA intervention (P>0.05). EA of GV20, GV16 and BL23 can effectively improve the learning-memory ability in AD mice, which may be related to its function in inhibiting neuronal apoptosis in the hippocampus and down-regulating the expression levels of Aβ, Caspase 3 and Bax proteins in both hippocampus and cerebral cortex.