KA诱发癫痫反复发作损伤大鼠空间学习记忆及中脑多巴胺能神经元

目的探讨颞叶癫痫反复发作(Spontaneous recurrent se izure,SRS)对大鼠空间学习记忆影响及中脑内多巴胺能神经元变化。方法以红藻氨酸(kain ic ac id,KA)制备颞叶癫痫大鼠模型,以是否出现SRS为标准将KA大鼠分为伴有反复发作和不伴有反复发作组,盐水为对照组。分别进行水迷宫行为测试,评价其学习记忆能力;并用酪氨酸羟化酶(Tyrosine hydroxylase,TH)免疫组化方法来观察各组大鼠中脑内多巴胺能神经元变化。结果KA处理后,按照Rac ine描述标准,KA组动物发作全部达到4~5级。KA后3周大鼠19只出现SRS,16只未见SRS;Morris水迷宫发现,在5 d的空间学习记忆测试中,反复发作KA大鼠的寻找潜伏期明显长于不伴有SRS的KA大鼠和盐水对照组(P<0.01),而不伴有SRS组与盐水对照组没有明显差别;伴有SRS的KA组大鼠总共穿过平台次数显著少于不伴有SRS的KA组大鼠和盐水对照组(P<0.01)。TH免疫组织化学结果发现与不伴有SRS的KA大鼠和盐水对照组比较,伴有SRS的KA大鼠在腹侧被盖的多巴胺能神经元大量脱失(P<0.01)。结论KA大鼠癫痫反复发作可能与空间学习记忆障碍和在腹侧被盖多巴胺能神经元大量脱失相关。

Spontaneous recurrent seizure induced by KA damages spatial learning and memory as well as dopaminergic neurons in rats

Objective To explore the effects of Spontaneous recurrent seizure(SRS) on Spatial learning memory and dopaminergic neurons of the midbrain in KA treated rats.Methods The rats were injected with a convulsive dose(10 mg/kg,s.c.) of KA to establish an acute seizure model and were selected as the SRS rats according to the scale of Racine in the following 3 weeks.Morris water maze was used to evaluate cognitive function in the animals.We used tyrosine hydroxylase(TH)-immunohistochemistry to measure the immunoreactivity(IR) of the dopaminergic neurons in the midbrain of the rats.Results All KA treated rats were in the stages from 4 to 5 according to the scale of Racine.After 3 weeks,19 KA treated rats showed SRS,but not Morris water maze results showed that during five days of learning memory training and testing,the search latency of KA(treated rats) with SRS was much longer than that of KA treated rats without SRS and saline treated rats significantly(P<0.01).In theprobe test,KA treated SRS rats crossed the location of platform only 5 times,which was much less than that of the KA treated rats without SRS and saline treated rats,respectively(P<0.01,(P<0.01)).TH immunohistochemistry showed that compared with KA treated rats without SRS and saline treated rats,the KA treated SRS rats lost more of TH-IR positive dopaminergic neurons in VTA(P<0.01).Conclusion Spatial learning memory deficits could be induced by SRS;the loss of dopaminergic neurons in VTA was associated with the learning memory deficits induced by SRS in KA treated rats.