摘要
目的慢性脑低灌注(chronic cerebral hypoperfusion,CCH)可导致认知功能的损害。丰富环境(enrich edenvironment,EE)可通过改善突触可塑性而提高学习和记忆能力。到目前为止EE对CCH所导致的认知功能损害的影响还不明确。为了进一步研究EE对CCH认知功能损害的影响,本科进行了EE对CCH所导致的认知功能损害和突触可塑性影响的研究。方法健康成年雄性Wistar大鼠被随机分为3组:假手术组(sham组),CCH组和CCH+EE干预组。检测各组大鼠的空间学习记忆能力,海马CA1区的长时程增强(long-term potentiation,LTP)、输入-输出关系曲线和双脉冲异化(paired-pulse facilitation,PPF)以及突触相关蛋白的表达水平变化。结果①EE干预可改善CCH所导致的大鼠空间学习记忆功能的损害。②与假手术组比较(195.5%±11.2%),CCH组大鼠的LTP发生显著的下降(128.6%±6.8%,P<0.01)。给予EE干预的CCH大鼠(176.4%±9.4%)LTP出现明显的增加(P<0.01)。③假手术组与CCH组的输入-输出关系曲线和PPF无明显差别(P>0.05)。当给予EE干预后也无显著性差异(P>0.05)。④CCH组大鼠的磷酸化环磷酸腺苷反应元件结合蛋白(phosphorylated cAMP responsive element binding protein,pCREB)的表达与假手术组比较下降了47%(P<0.01),而CCH+EE组的pCREB的表达是CCH组的177%(P<0.01)。对于CCH大鼠的突触素和微管相关蛋白-2(microtubule-associated protein2,MAP-2)的表达与假手术组比较分别减少了23%和29%(分别为P<0.05和P<0.01)。经过EE干预后CCH+EE组的突触素和MAP-2的表达与CCH组比较分别增加了31%和60%(分别为P<0.05和P<0.01)。结论 EE可改善CCH所导致的空间学习记忆功能和突触可塑性的损害,但不影响其基础传递效率和突触前的递质释放的概率。EE对CCH认知功能的改善可能源于其对突触后蛋白的调节起作用。
Objective Chronic cerebral hypoperfusion (CCH) could lead to cognitive impairment. An enriched environment (EE) improves learning and memory by improving synaptic plasticity. The impact of an EE on cognitive impairment induced by CCH is not, however, well known. To investigate this possible effect, we studied EE effects on cognitive impairment and synaptic plasticity following CCH. Methods Male Wistar rats were randomly divided into three groups: a sham-operated group (sham group), a cerebral hypoperfusion group (CCH group), and a cerebral hypoperfusion group that was also exposed to the EE (CCH+EE group). Spatial memory performance, Long-term potentiation (LTP), input-output curves, paired-pulse facilitation (PPF) and synaptic proteins of three groups were measured. Results ① EE treatment reversed spatial memory deficits induced by CCH. ② LTP was dramatically reduced in the CCH rats (128.6%±6.8%) as compared with sham-operated controls (195.5%±11.2%, P<0.01). In CCH rats that had been exposed to the EE, LTP was significantly increased (176.4%±9.4%, P<0.01). ③ No distinguishable difference of input-outputcurves and PPF between sham-operated rats and the CCH group (P>0.05). After exposure to the EE, they were not significantly changed (P>0.05). ④ pCREB expression was reduced by 47% in the CCH group as compared with that of the sham-operated group (P<0.01). The expression of pCREB in the CCH+EE group was 177% as compared with that of the CCH group (P<0.01). The expression of MAP-2 and synaptophysin was reduced by 23% and 29%, respectively, in the CCH group as compared with the sham-operated group (P< 0.05 and P<0.01, respectively). The expression of MAP-2 and synaptophysin increased by 31% and 60% in the CCH+EE group as compared with the CCH group (P<0.05 and P<0.01, respectively). Conclusion EE improved CCH-induced spatial cognitive impairment and synaptic plasticity injury without affecting basal synaptic transmission or the release probability of presynaptic neurotransmitters. The EE effect probably resulted from the regulation of postsynaptic potentiation.
出处
《中国医学前沿杂志（电子版）》
2012年第10期20-27,共8页
Chinese Journal of the Frontiers of Medical Science(Electronic Version)
基金
湖北省自然科学基金(2009CDA077)
关键词
丰富环境
慢性脑低灌注
突触可塑性
认知功能损害
Enriched environment
Chronic cerebral hypoperfusion
Synaptic plasticity
Cognitive impairment
