尼莫地平改善高钙所致记忆障碍的脑内突触机制

海马内微量注射高钙造成小鼠记忆障碍后，观察了尼莫地平（腹腔注射）对记忆障碍的改善作用，并用透射电镜和图像分析仪对海马CA3区Gray I型突触界面结构参数进行了观测和定量分析，进一步探讨尼莫地平改善高钙所致记忆障碍的脑内突触机制。结果表明，尼莫地平确能改善高钙所致记忆障碍，并能显著逆转高钙所致的小鼠海马CA3区突触间隙宽度显著增大，PSD极显著变薄，平坦型突触显著增多，凹型和穿孔型突触显著减少等一系列突触界面结构的病理性变化。提示海马CA3区Gray I型突触界面结构参数的逆转可能是钙拮抗剂尼莫地平改善高钙所致记忆障碍的形态学基础

The Synaptic Mechanisms of Nimodipine in Ameliorating the CaCl2-Induced Memory Dysfunction in Brain

Overloading of intracellular Ca2 in the brain might be responsible for the occurrence of some brain dysfunctions.Nimodipine,a dihydropyridine calcium channel antagonist,has a potent vasodilatory effect on expanding cerebral vessels and increasing cerebral blood flow.It is also able to block the voltage-dependent L-type channels.Its antiepileptic properties have been shown in various animal models,including Ca2 -induced seizures in adult mice and rats.As a result,there has been a great deal of interest in potential beneficial effects of nimodipine on CNS function.Several lines of investigation have shown that nimodipine administration is beneficial in brain dysfunction associated with trauma or aging.The purpose of the present study was to further investigate the synaptic mechanisms of nimodipine in ameliorating CaCl_2-induced memory dysfunction in brain.Male Kun Ming mice were divided into 3 groups: control(n=10),CaCl_2 group(n= 12),and CaCl_2 nimodipine group(n = 11).These groups were injected with physiological saline(intrahippocampally),CaCl_2(2.9ug per mouse,treated intrahippocampally),CaCl_2(2.9ug per mouse,treated intrahippocampally) and nimodipine(2ug per mouse,ip),respectively.Memory retention was assessed using a one-trial passive avoidance response task.After the experiment,the animals were killed and the hippocampus of each was prepared for transmission electron microscopy.The structural parameters of the Gray I synaptic interface in the hippocampal CA_3 areas of mice were observed and analyzed quantitatively by a transmission electron microscope and XY-biological image analysis system.The main results were as follows: (1) Compared to that of the control group,the STL of the CaCl_2 group was greatly shortened in one trial passive avoidance response(p<0.01).The thickness of postsynaptic density(PSD) of this group was thinned significantly (p<0.001).The width of the synaptic cleft showed a robust increase(p<0.01).The number of the flat synapses was significantly increased(p<0.05),while the numbers of the negative curve synapses and perforated synapses were also reduced(p<0.05). (2) Compared to that of the CaCl_2 group,the STL of CaCl_2 nimodipine group was long in one trial passive avoidance response(p<0.01),indicating that nimodipine was able to ameliorate chemical memory dysfunction.Accordingly,there were the reverse changes of the structural parameters of the Gray I synaptic interface in the CaCl_2 nimodipine group compared with the above-mentioned pathological changes in the CaCl_2 group.The treatment of nimodipine was able to antagonize the pathological morphology changes caused by CaCl_2. These results suggest that the reverse of the structural parameters of the Gray I synaptic interface in the hippocampal CA_3 areas might be the morphological foundation of the amelioration of calcium antagonist-nomodipine on memory deficit caused by the injection of CaCl_2.However,further experimental studies are needed to investigate the mechanisms of nimodipine in ameliorating CaCl_2-induced memory dysfunction in the brain.