急性高原低氧对小鼠学习记忆及海马CA1区PKA、CREB表达的影响

THE INFLUENCE OF ACUTE HIGH ALTITUDE HYPOXIA ON LEARNING AND MEMORY AND HIPPOCAMPAL CREB,PKA EXPRESSION IN MICE

目的初步探讨急性高原低氧对小鼠学习记忆能力以及海马CA1区PKA、CREB表达的影响。方法将小鼠随机分为两组:高海拔对照组(青海省西宁地区,海拔2361米)、急性高原组(青海省果洛州花石峡地区,海拔4300米)。两组小鼠在不同海拔均喂养5天后,应用跳台实验观察小鼠训练时的潜伏期及错误次数,评估急性高原低氧对小鼠学习记忆能力的影响;两组小鼠在不同海拔均喂养8天后断头取脑,通过免疫组织化学法半定量观察海马区环磷酸腺苷反应元件结合蛋白(c AMP response element—binding protein,CREB)、蛋白激酶A(PKA)的表达。结果急性高原组跳台实验潜伏期显著短于高海拔对照组(P<0.05),且错误次数显著增多(P<0.05);CREB及PKA主要在海马CA1区表达,且急性高原组表达量明显低于高海拔对照组(P<0.05)。结论急性高原低氧可能使小鼠学习记忆能力下降,其作用机制可能与CREB、PKA表达降低导致c AMP-PKA-CREB通路障碍有关。

Objective To investigate the effect of learning and memory, in particular, the CREB, PKA expres- sion of hippocampal neurons in mice under stressed by acute high altitude hypoxia. Methods The mice were ran- domly divided into two groups and reared to different altitude environment, control group（ Xining of Qinghai, at 2361 meters above sea level） ; acute high altitude group （ the Golok Huashixia County of Qinghai, at 4300 meters above sea level）. After fed both groups mice for 5 days at different altitudes ,we applied step down test to observe the incu- bation phase and the number of errors for training the influence of acute altitude hypoxia on learning and memory in mice ; Moreover,we used immunohistochemieal method to explore the CREB, PKA expression changes of hippocam- pal neurons. Results The result of step down test showed that the acute altitude group incubation phase significantly shorter than control group（P 〈 0.05 ）, and the number of errors was significantly increased in acute nigh altitude group（ P 〈 0.05 ） ;the expression of CREB, PKA main in CA1 hippocampus area, and the acute high altitude group was significantly lower than in the control group（ P 〈0.05 ）. Conclusion Acute altitude hypoxia may induce learn- ing and memory decline in mice and the mechanism may be related to the decrease expression of CREB, PKA, which may induce the disorders of cAMP - PKA - CREB pathway.