游泳运动对去卵巢大鼠学习记忆能力和海马APP、NR1 mRNA的影响
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摘要
学习与记忆是脑的高级活动之一。海马在空间学习和记忆过程中起重要作用,损伤海马将会影响空间学习与记忆的能力。研究表明,核心亚基NR1是NMDA受体行使功能的基本单位NR1/NR2复合体的必需部分,NR1在新事物探悉实验和空间学习记忆过程中有重要的作用。雌激素的缺失将会导致空间认知学习记忆能力的下降,并伴随NR1表达的减少。在更年期妇女中,雌激素的缺失是引发神经退行性病变的重要原因之一,而临床观察或回顾性研究发现,雌激素的缺失会引起β-淀粉样蛋白的沉淀,后者成为形成阿尔茨海默病(AD)病的主要原因。近年来,生长的机体研究表明,适宜的自主运动对学习记忆能力的提高有良好的促进作用,有助于大脑相关脑区神经元的增殖、存活和分化,以及相关蛋白的表达,并与减少神经退行性病变发生的相对危险性相联系。有研究发现,运动与雌激素在脑的有关区域发生相互作用(CROSS talking)。本研究对成年去卵巢雌性SD大鼠进行8周无负重自主游泳运动后,进行新异物体探测测试和Y迷宫行为学学习记忆能力测试,并对海马内APP和NR1 mRNA等相关分子生物学指标进行检测。
     实验筛选出38只大鼠随机分为假手术对照组(SH-CT,n=9),假手术运动组(SH-EX,n=9),去卵巢对照组(OVX-CT,n=10)和去卵巢运动组(OVX-EX,n=10)。SH-EX组和OVX-EX组进行8周无负重游泳运动,SH-CT组和OVX-CT组每次给与水的刺激,在运动的第六周进行新异物体探测测试,在运动的第7周测试Y迷宫学习情况,运动的第8周测试记忆情况。最后一次运动完24小时后,取左右海马样本组织,用RT-PCR方法检测APP、NR1mRNA的表达水平。
     结果如下:
     1.游泳运动或雌激素的缺失没有对新异物体探测产生显著性差异(p>0.05),对Y迷宫的测试,雌激素的缺失将导致学习和记忆能力的下降,而游泳运动会在一定程度上弥补这种认知障碍。
     2.雌激素的缺失导致对海马内APP和NR1 mRNA的表达下降,而游泳运动对海马内APP和NR1 mRNA的表达有所上调。
     结论:
     正常生理浓度的雌激素对空间认知功能有重要的作用,雌激素的缺失会导致大鼠对空间学习记忆能力的下降,同时伴有海马NR1、APP mRNA表达的下降,而游泳运动作为一种外在的刺激手段,会在一定程度上弥补因雌激素的缺失导致的认知障碍。
Learning and memory are the advanced activities of brain.Hippocampus plays an important role in spatial learning and memorizing.The injury of hippocampus will influence the ability of spatial learning and memorizing.Studies show that core subunit NR1 is the necessary part of NR1/NR2 complex which is the basic unit for NMDA function.NR1 plays an important role in the novel object recognition task and the spatial learning and memorizing.Lack of estrogen weakens the ability of spatial learning and memorizing and decreased NR1 expression.Lack of estrogen is the important reason causes degenerative disease in menopause women.Clinical observation and restrospective study find lack of estrogen causeβ-amyloid denaturation which is the main reason of AD disease.Recently,studies about developing body show moderate voluntary activity may promote the ability of spatial learning and memorizing and are helpful for brain neuron proliferation,survival and differentiation as well as related protein expression which are associated with the decreased risk of degenerative diseases.Studies show that there is cross talk between exercise and estrogen in brain domain.The current study designed to probe the effects of 8 weeks weightless swimming training on the ability in novel object recognition task and Y maze learning as well as the gene expression of APP and NR1 in Hippocampus for bilateral ovariotomy rats.
     38 female rats were included in this study and were divided into 4 groups,which included sham-operation group(SH-CT,n=9),sham-operation and exercise group (SH-EX,n=9),ovariotomy group(OVX-CT,n=10)and ovaritomy and exercise group (OVX-EX,n=10).SH-EX and OVX-EX groups did 8 weeks weightless swimming while SH-CT and OVX-CT were exposed to water stimulations the same times.In the sixth week,all the rats did the novel object recognition task and in the seventh and eighth week Y maze learning test and memory test respectively.24 hours after the last time exercise,all rats were killed and hippocampus were saved for testing APP and NR1 mRNA expression through RT-PCR method.
     Results:
     1.Neither swimming training nor lack of estrogen leaded to significant change in the novel object recognition task(p>0.05).Lack of estrogen weakened the ability to learn and memorize and swimming training prevent the cognitive disorder to some extent.
     2.Lack of estrogen decreased the mRNA expression of APP and NR1,but swimming training increased them.
     Conclusion:
     Normal level of estrogen was very important for spatial learning and memorizing which were associated with NR1 and APP mRNA expression decrease.However, exercise,as a kind of exogenous stimulation to the body,can prevent the cognitive disorder caused by lack of estrogen.
引文
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