老年大鼠海马细胞凋亡和神经元信号转导通路的变化与学习记忆的关系

Relationship between learning and memory ability and the changes of signal transduction pathway and apoptosis of hippocampal neurons of old rats

目的研究海马细胞凋亡、神经元信号转导通路在老年大鼠大脑中的变化及其与学习记忆的关系。方法选用8月龄和24月龄大鼠,利用Y迷宫测定大鼠学习记忆能力;TUNEL法检测其海马区神经元凋亡;免疫组织化学染色和SDS聚丙烯酰胺凝胶转移电泳检测PI3K、p-PI3K、AKt、p-AKt和Caspase-9p35的表达水平。结果老年大鼠与青年鼠相比,学习尝试次数明显增加,记忆正确次数明显减少;海马区可见到较多TUNEL阳性神经元;p-PI3K和p-AKt的活性明显降低,Caspase-9p35的表达明显增加;PI3K和AKt的表达在两组之间没有明显变化。结论老年大鼠学习记忆能力下降与海马细胞凋亡及PI3K-AKt-Caspase-9信号转导通路的障碍有关。

Objective To investigate the relationship between the changes of signal transduction pathway, neuronal apoptosis and learning and memory ability in old rats. Methods Eight-month-old and twenty-four-month-old rats were used in the study. Y-electric maze was used to detect learning and memory ability of rats. TUNEL method was used to detect apoptosis of hippocampal neurons. Immunohisto- chemistry staining and Western blotting were used to detect the expressions of PI3K, p-PI3K, p-AKt, AKt and Caspase-9p35. Results Compared with young rats, the old rats showed their disorders of learning and memory ability. Neurons in hippocampal subfield exhibited TUNEL positive cells. Expressions of p-PI3K and p-AKt were depressed while Caspase-9p35 was increased. There was no marked change of PI3K and AKt between old and young groups. Conclusions Decrease of learning and memory ability in old rats is positively correlated with the increase of hippocampal neuronal apoptosis and the obstructed signal transduction pathway.