Effect of electroacupuncture intervention on the spinal cord PPIA/NF-κB signaling pathway in mice with amyotrophic lateral sclerosis. / ç”µé’ˆå¯¹è‚ŒèŽç¼©ä¾§ç´¢ç¡¬åŒ–ç—‡å°é¼ è„Šé«“PPIA/NF-κB信号通路的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on motor function, expression of extracellular cyclophile A(PPIA) and PPIA/nuclear factor-κB (NF-κB) signaling pathway in spinal cord of amyotrophic la-teral sclerosis (ALS) mice, so as to explore the mechanism of EA intervention in regulating extracellular PPIA on neuroinflammation in ALS mice. METHODS: Thirty ALS-SOD1G93A mice with hSOD1-G93A gene were randomly divided into model, EA and Riluzole groups , with 10 mice in each group, and other 10 ALS-SOD1G93A negative mice were used as the blank group. EA was applied to bilateral "Yanglingquan"(GB34) and "Zusanli"(ST36) for 20 min once daily, 5 days a week for 2 weeks. In the Riluzole group, riluzole solution (30 mg·kg-1·d-1) was administrated intragastrically, and the treatment time was the same as that in the EA group.Rotating rod experiment and open field experiment were used to evaluate the changes in motor function of mice .The morphology of motor neurons in the anterior horn of spinal cord was observed by HE staining.The relative protein expression levels of PPIA, TDP-43 and NF-κB in the spinal cord were detected by Western blot.The positive expression level of TDP-43 in the spinal cord was detected by immunohistochemistry. The positive expression level of PPIA in spinal cord was marked by immunofluorescence. Serum PPIA content was determined by ELISA. RESULTS: Compared with the blank group, the time of rod dropping and the total distance of open field movement in the model group were shortened (P<0.01), the number of motor neurons in the anterior horn of the spinal cord was reduced, the cell morphology was incomplete, the cell body was atrophied, the protein expression and positive expression of TDP-43 were increased (P<0.01), the protein expressions of PPIA and NF-κB in the spinal cord were increased(P<0.01), the serum content of PPIA and immunofluorescence expression of PPIA in spinal cord were increased (P<0.01). Compared with the model group, the time of rod dropping and the total distance of open field movement of mice in the EA group and the Riluzole group were prolonged (P<0.05, P<0.01), and the injury of motor neuron in the anterior horn of the spinal cord was decreased, the protein expression and positive expression of TDP-43 in the spinal cord were decreased (P<0.05, P<0.01)；the relative expression levels of PPIA and NF-κB proteins were decreased (P<0.05, P<0.01), and the content of PPIA in serum and the immunofluorescence expression of PPIA in the spinal cord were decreased (P<0.05, P<0.01) in the EA group；the relative protein expression of NF-κB and fluorescence expression of PPIA in spinal cord of mice in the Riluzole group were decreased (P<0.05). CONCLUSIONS: EA intervention can improve motor function in ALS mice, and its mechanism may be related to the inhibition of PPIA/NF-κB signaling pathway by EA to alleviating neuroinflammatory response.

[Effect of electroacupuncture on hippocampal synaptic plasticity and complement dependent memory impairment in Parkinson's disease dementia mice].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Xiusanzhen" ï¼»bilateral "Yingxiang"(LI20)+"Yintang"(GV24+)ï¼½ on synaptophysin (SYN), postsynaptic density protein-95 (PSD-95), Iba-1+ CD68+ microglia and complement C related protein expression of hippocampus in Parkinson's disease dementia (PDD) mice, so as to explore its mechanism in improving memory impairment of PDD. METHODS: Male C57BL/6 mice were randomly divided into control, sham operation, model and EA groups, with 10 mice in each group. The PDD model was established by injecting 6-OHDA into the medial forebrain tract. EA (2 Hz, 1 mA) was applied to unilateral LI20 and GV29 for 20 min once daily for consecutive 14 days. Morris water maze and new object recognition test were used to evaluate the learning and memory ability. Western blot was used to detect the expression of SYN and PSD-95 proteins in hippocampus. Immunofluorescence was used to label Iba-1+ CD68+ microglia and C1q positive cells in hippocampal CA1 region. The content of C3 protein in hippocampus was detected by ELISA. RESULTS: Compared with the control group, there was no statistical significance in all the observed indexes in the sham operation group. Compared with the sham operation group, the average escape latency (AEL) prolonged significantly (P<0.01), the target platform crossing times (TPCT) and new object recognition index (NORI) decreased remarkably (P<0.01); the expressions of SYN and PSD-95 proteins in hippocampal CA1 region were significantly decreased (P<0.01); the rate of Iba-1+CD68+ microglia, the rate of C1q positive cells and the content of C3 protein were significantly increased (P<0.01) in the model group. In comparison with the model group, the AEL was shortened (P<0.01), the TPCT and NORI were increased (P<0.05) remarkably; the expressions of SYN and PSD-95 proteins in hippocampal CA1 region were increased (P<0.01, P<0.05); the rate of Iba-1+ CD68+ microglia, the rate of C1q positive cells and the content of C3 protein were significantly decreased (P<0.01) in the EA group. CONCLUSION: "Xiusanzhen" can alleviate the learning and memory impairment of PDD model mice, and improve the synaptic plasticity of hippocampal CA1 area. The mechanism may be related to the reduction of C1q and C3 deposition in hippocampal CA1 region and the reduction of microglia phagocytosis.