| ABSTRACT:Background:To clarify the molecular pathway of Tongdu yupi tiaoshen electroacupuncture in regulating mitochondrial function and improving cognitive deficits in rats with CFS cognitive impairment.Objective: To observe the effects of Tongdu yupi tiaoshen electroacupuncture on mitochondrial division and mitochondrial autophagy in the hippocampal CA1 region of rats with CFS cognitive impairment.Methods:CFS cognitively impaired rats were prepared by chronic fatigue multifactorial compound stress method for 35 consecutive days, and then randomly divided into 10 rats each in model group, and electroacupuncture group,10 healthy male SD rats for the control group.During the treatment period, the control group was kept normally, the model group was given continuous modeling stimulation, and the electroacupuncture group was given electroacupuncture treatment based on continuous modeling at the GV24 puncture GV20 and the GV14, with a continuous wave, frequency of 10 Hz, and the current was applied for 15 min/times/day, for 28 consecutive days. The general condition semi-quantitative observation scale and morris water maze were used to evaluate the general condition and, learning and memory ability of rats in each group; transmission electron microscopy(TEM) was used to observe the ultrastructural changes of mitochondria in the CA1 region of the hippocampus of rats in each group; and autophagy and Pinkink, a key functional molecule of mitochondria, were detected in the mitochondrial autophagy and mitochondrial autophagy in the CA1 region of hippocampus of rats in each group using ELISA, Western Blot and RT-qPCR. Western Blot, and RT-qPCR were used to detect mitochondrial autophagy in the CA1 region and the protein and mRNA expression levels of key mitochondrial molecules Pink1, Parkin, and Drp1. Results:After modeling, compared with the control group, the general condition score of the modeling group was significantly higher (P<0.05), all scores were ≥4, the escape latency was prolonged (P<0.05), and the number of crossing the platform was reduced (P<0.05), which met the success criteria of modeling. After the treatment, compared with the control group, the general condition score of the model group continued to increase (P<0.05), the escape latency was prolonged (P<0.05), and the number of crossing the platform decreased (P<0.05),the mitochondrial destruction in the CA1 region of the hippocampus increased, the morphology was swollen or shrunken, the matrix became lighter and accompanied by vacuolation, the cristae disappeared, the outer mitochondrial membrane was incomplete, and autophagosomes appeared, the expression levels of Pink1, Parkin, and Drp1 protein and mRNAwere decreased in the model group (P<0.05). After treatment, the general condition score of the electroacupuncture group decreased,all scores were＜4; the escape latency was shortened and the number of crossing the platform increased, compared with the model group, there was a statistically significant difference (P<0.05) .Compared with the control group, the number of mitochondria destroyed and the number of autophagosomes in the CA1 region of the hippocampus in the electroacupuncture group was smaller, the morphology was slightly swollen, the inner crest was clearer, the cristae were broken but the cristae did not disappear, the outer membrane was roughly intact, and the matrix was not significantly changed, the expression levels of Pink1, Parkin, and Drp1 protein and mRNA in the electroacupuncture group were up-regulated (P<0.05).Conclusion:Tongdu yupi tiaoshen electroacupuncture has anti-fatigue and cognitive-enhancing effects, which may be related to the regulation of mitochondrial autophagy and mitochondrial fission functions in CFS cognitive impairment rats. |