ABSTRACT
OBJECTIVE: To investigate the effect of electroacupuncture on the P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau pathway in rats with Alzheimer's disease (AD), as well as the mechanism of electroacupuncture in the prevention and treatment of AD. METHODS: Sprague-Dawley rats were randomly divided into control group, sham-operation group, model group, and electroacupuncture treatment group, with 12 rats in each group. A rat model of AD was established by injection of Aβ25-35 into the bilateral hippocampus. The rats in the electroacupuncture treatment group were given electroacupuncture at "Baihui" (GV20) and "Shenshu" (BL23) once a day, 15 min each time, for 10 days. Morris water maze was used to evaluate learning and memory abilities, immunohistochemistry was used to measure the distribution and expression of P35/P25, CDK5, and Tau5 in the hippocampus, and Western blot was used to measure the expression of the above mentioned proteins, phosphory-lated Tau(Ser199, Ser202). RESULTS: In the visual platform test, there were no significant differences in escape latency and search path between groups (P>0.05). In the hidden platform test, there were no significant differences in escape latency and search path between the control group and the sham-operation group (P>0.05); the model group had significantly longer escape latency and search path than the control group and the sham-operation group (P0.05). The model group had significantly higher protein expression of phosphorylated Tau(Ser199, Ser202) in the hippocampus than the control group and the sham-operation group (P<0.01, P<0.05). The electroacupuncture treatment group had significantly lower protein expression of phosphorylated Tau(Ser199，Ser202) than the model group (P<0.05, P<0.01). CONCLUSION: Electroacupuncture may delay the progression of AD by affecting the expression of proteins involved in the P35/P25-CDK5-Tau pathway in the hippocampus of rats.
ABSTRACT
Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenshu (BL23) acupoints on learning-memory ability and expression of the relative protein of P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau phosphorylation signaling pathway in the prefrontal cortex (PFC) in rats with Alzheimer's disease (AD), so as to reveal its potential mechanisms in treating AD. Methods:Male adult Sprague-Dawley rats were randomly divided into normal control group, sham group, model group and treatment group with six rats in each group. The AD model was constructed by bilateral hippocampal injection of Aβ25-35 in latter two groups. Equal amount of normal saline was injected into the sham group. The treatment group was acupunctured at Baihui and Shenshu once a day for ten days. All the rats were tested with Morris Water Maze. Immunohistochemistry staining and Western blotting were used to detect the related protein of P35/P25-CDK5-Tau protein phosphorylation in the PFC. Results:Compared with the normal control group and the sham group, the escape latency and escape length increased (P < 0.05) and the times crossing the platform reduced (P < 0.05) in the model group; compared with the model group, the escape latency and escape length reduced (P < 0.05), and the times crossing the platform increased (P < 0.05) in the treatment group. The optical density of P35/P25 and CDK5 were significantly higher in the model group than in the normal control group and the sham group (P < 0.01), and they were lower in the treatment group than in the model group (P < 0.001). The relative expression of P35/P25, CDK5, Tau[pS199] and Tau[pS202] were higher in the model group than in the normal control group and the sham group (P < 0.05), and the expression of the above proteins was lower in the treatment group than in the model group (P < 0.05). Conclusion:Electroacupuncture could improve the learning-memory and spatial exploration ability, which associate with inhabiting the P35/P25-CDK5-Tau protein phosphorylation signaling pathway in the PFC to delay the development of AD.
ABSTRACT
The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.