β-淀粉样蛋白诱导的阿尔茨海默病大鼠模型中BDNF与TRPC3的关系

摘要

目的 探讨经典瞬时受体电位通道蛋白3 (TRPC3)与脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)大鼠模型海马组织中的表达及其相互关系.方法将SD大鼠随机分为PBS组、AD组和AD+BDNF组.采用β-淀粉样蛋白(Aβ1-42)侧脑室注射,制备AD模型.BDNF在造模14 d后经侧脑室导管注入.Morris水迷宫实验测定大鼠的空间学习记忆能力.实时PCR和Western blotting分别检测海马组织中TRPC3和BDNFmRNA和蛋白的表达情况.结果Morris水迷宫实验表明,AD组大鼠第5天逃避潜伏期较PBS组延长(P＜0. 05);AD+BDNF组大鼠的逃避潜伏期较AD组缩短(P＜0. 05).实时PCR及Western blotting结果表明,与PBS组相比,TRPC3和BDNF mRNA和蛋白在AD组表达均降低(P＜0. 05);与AD组相比,TRPC3 mRNA和蛋白在AD+BDNF组表达均增高(P ＜0. 05).结论BDNF和TRPC3在AD大鼠海马组织表达降低;外源性BDNF可能通过上调TRPC3表达,从而改善Aβ142导致的AD大鼠空间学习记忆障碍,起到保护神经元的作用.%Objective To investigate the expression and relationship of canonical transient receptor potential channel-3 (TRPC3) and brain-derived neurotrophic factor (BDNF) in the hippocampus of a rat model of Alzheimer's disease (AD). Methods SD rats were randomly divided into PBS, AD, and AD+BDNF experimental groups. AD models were generated by intracerebroventricular injection ofβ-amyloid protein (Aβ1-42). BDNF was injected via the lateral ventricle catheter after 14 days. The Morris water maze test was used to assess the spatial learning and memory ability of the rats. The expression of TRPC3 and BDNF mRNA and protein in the hippocampus were detected by RT-PCR and Western blotting, respectively. Results The Morris water maze test showed that the escape latencies of the fifth day in the AD group were longer than those in the PBS group (P ＜ 0. 05). The escape latencies in the AD+BDNF group were shorter than those in the AD group (P ＜ 0. 05). RT-PCR and Western blotting results showed that the expression of both TRPC3 and BDNF were reduced in the AD group compared with the PBS group (P ＜ 0. 05). TRPC3 expression was increased in the AD+BDNF group compared with the AD group (P ＜ 0. 05). Conclusion The expression of BDNF and TRPC3 is decreased in the hippocampus of AD rats. An exogenous BDNF injection appears to improve the spatial learning and memory of AD rats that are impaired by a Aβ1-42 injection, possibly via TRPC3 upregulation, and may play a protective role in neurons.