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出 处:《中国药理学通报》2015年第B11期69-69,共1页Chinese Pharmacological Bulletin
摘 要:Aim To investigate whether Kv7 channels opener retigabine could alleviate memory impairment induced by chronic restraint stress (CRS) and the underlying neuroprotective mechanisms. Methods Adult male Kunming (KM) mice, weighing 20 - 25 g, were restrained in well-ventilated Plexiglass tubes for 6 h daily beginning from 10 : 00 to 16 : 00 for 21 consecutive days. Mice were injected with retigabine ( 10 mg · kg^-1) or vehicle ( 10% DM- SO) 30 rain before restraint stress for 21 days. After stressor cessation, the spatial learning and memory was deter- mined by Morris water maze test, the levels of p-Akt, p-GSK-3β and p-Erkl/2 of hippocampal tissues were exam- ined by western blot. Results Compared with control group, CRS mice exhibited significantly longer escape laten- cies on day 2, 3 and 4 (P 〈 0.05, P 〈 0. 01, P 〈 0.01 ) respectively, but retigabine ( 10 mg · kg^-1) treatment had no influences on escape latencies compared with CRS group. During the probe test, CRS mice spent significant less time in target quadrant than control group (P 〈 0.01 ). Compared with CRS group, retigabine ( 10 mg · kg^-1 ) treatment increased the time spent in target quadrant (P 〈 0.01 ). Additionally, the swimming speed showed no significant differences among groups. Western blot results showed that the levels of p-Akt, p-GSK-3β and p-Erkl/ 2 in the hippocampus of CRS mice were significantly decreased compared with control group. Compared with CRS group, retigabine ( 10 mg· kg^-1) treatment strongly prevented the reduction of p-Akt and p-GSK-3 β (P 〈 0.01 ), but had no effect on the reduction of p-Erkl/2. Conclusion Retigabine protected against CRS-induced spatial memory retrieval impairment partly via activation of Akt/GSK-3β signaling pathway.
关 键 词:RETIGABINE chronic RESTRAINT stress (CRS) memory HIPPOCAMPUS Akt/GSK-3β
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