发育期大鼠反复痫性发作后远期学习记忆障碍及海马神经元可塑性的研究

Long-term effects on learning and memory and hippocamus neuroplasticity in immature rats following recurrent seizures

目的探讨发育期大鼠反复痫性发作对大鼠成年后学习记忆及海马神经元可塑性的影响。方法生后10 dSD大鼠32只,随机分为实验组16只和对照组16只。实验组用戊四氮(PTZ)反复腹腔注射5 d,制成反复痫性发作模型,对照组腹腔注射等量生理盐水。在生后第60天用Morris水迷宫评价大鼠的学习记忆功能,用RT-PCR方法检测大鼠海马神经元可塑性标志物神经生长相关蛋白-43(GAP-43)mRNA的表达变化。结果与对照组比较,实验组在Morris水迷宫测试中平均逃避潜伏期明显延长(P<0.05),原平台所在象限的游泳时间明显缩短(P<0.05);海马组织GAP-43 mRNA的表达显著增多(P<0.05)。结论发育期大鼠反复痫性发作可引起远期学习记忆损害及海马神经元激活和突触重建等神经元可塑性改变,而GAP-43表达增多可能是学习记忆功能和可塑性变化的分子机制。

Objective To explore the effects of recurrent seizures in immature rats on learning and memory and hippocamus neuroplastieity when the animals were in adulthood. Methods Rats at postnatal day 10 （n = 32） were divided into experimental group （n = 16） and control group （n = 16）. Rats in the experimental group were treated with pentylenetetrazol （PTZ） daily by intraperitoneal injection for 5 consecutive days to induce recurrent seizure and rats in the control group were injected with normal saline for 5 consecutive days. All rats at postnatal day 60 were tested for spatial learning and memory by Morris water maze task. The expressions of GAP- 43mRNA,the marker for neuroplasticity in hippocampus were detected by reverse transcription polymerase chain reaction. Results In the experimental group, the mean escape latency of searching the platform significantly prolonged （ P 〈 0.05 ） and swimming time in the original platform region significantly shortened （P 〈 0.05 ） in Morris water maze. The expression of GAP-43 mRNA in hippocampus in the experimental group was significantly increased than that in the control group （ P 〈 0.05 ）. Conclusion These findings indicate that recurrent seizure in immature rats have long-term detrimental effects on learning and memory and changes of hippocamus plasticity, such as synaptic reoganization and the action of neuron. GAP-43 increasing may be the molecular mechanisms for learning and memory and hippocamus neuroplasticity.