[Effect of electroacupuncture at "Baihui" (GV20) and "Shenting" (GV24) on cognitive impairment and mitochondrial energy metabolism in vascular dementia rats].

Abstract

Objectives: To observe the effect of electroacupuncture(EA) on adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and mitochondrial energy metabolism in vascular dementia (VD) rats, so as to investigate its potential mechanisms underlying prevention and treatment of VD.

Methods: Male SD rats were randomly divided into sham surgery group, model group, EA group, non-acupoint group, and EA+inhibitor group, with 8 rats in each group. Except for the sham surgery group, VD model was established in other 4 groups by permanent bilateral common carotid artery ligation. Rats in the EA group received EA at "Baihui"(GV20) and "Shenting"(GV24), while rats in the non-acupoint group received EA at the non-acupoint 10 mm above the iliac crest bilaterally. The EA frequency was 2 Hz/15 Hz, duration was 30 min per session, once a day, for 7 d continuously. Rats in the EA+inhibitor group received intraperitoneal injection of AMPK inhibitor Compound C 2 h before EA intervention. After intervention, Morris water maze test was used to evaluate the learning and memory ability of rats. ELISA was used to detect the contents of mitochondrial complexes I-IV in the hippocampus. Colorimetric method was used to detect the content of adenosine triphosphate (ATP) in the hippocampus. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Western blot was used to detect the protein expressions of hippocampal AMPKα1, fatty acid translocase (FAT)/cluster of differentiation 36 (CD36), and acetyl-CoA carboxylase 2 (ACC2).

Results: Compared with the sham surgery group, the escape latency and total distance traveled of rats in the model group increased (P<0.01), while the time spent in the target quadrant and the number of original platform crossings decreased (P<0.01). The contents of mitochondrial complexes I-IV and ATP in the hippocampus decreased (P<0.01), mitochondrial structure was severely damaged, and the expressions of hippocampal AMPKα1, FAT/CD36 proteins decreased (P<0.01), while ACC2 expression increased (P<0.01). Compared with the model group, the escape latency and total distance traveled of rats in the EA group decreased (P<0.01), while the time spent in the target quadrant and the number of original platform crossings increased (P<0.01). The contents of mitochondrial complexes I-IV and ATP in the hippocampus increased (P<0.01), and the mitochondrial structure showed mild abnormalities. The expressions of hippocampal AMPKα1 and FAT/CD36 proteins increased (P<0.01), while ACC2 expression decreased (P<0.01), and the improvement in the EA group was better than that in the non-acupoint group and EA+inhibitor group (P<0.01). Correlation analysis showed that mitochondrial complex I content was negatively correlated with the escape latency and total distance traveled (P<0.0001), and positively correlated with the time spent in the target quadrant and the number of original platform crossings (P<0.05, P<0.0001).

Conclusions: EA can improve cognitive impairment in VD rats by activating AMPK, up-regulating FAT/CD36 expression, and down-regulating ACC2 expression, thereby promoting mitochondrial fatty acid metabolism and improving mitochondrial morphology and function.