摘要
为了观察快速衰老小鼠(senescence accelerated mouse,SAM)衰老过程中大脑额叶皮质中nNOS的分布和表达变化,探讨NO/nNOS在中枢神经系统衰老中的作用。采用雄性快速衰老亚系8小鼠(senescence accelerated mouse/prone8,SAMP8)及抗快速衰老亚系1小鼠(senescence accelerated mouse/resistance1,SAMR1)为研究对象,其中SAMP8为实验组,SAMR1为对照组,每组动物再分为青年组(2月龄)和老年组(10月龄)两组。用免疫组织化学方法观察SAM额叶皮质中的nNOS神经元的形态和分布,并计数nNOS阳性神经元在额叶皮质中的数量;用RT-PCR法检测额叶皮质中nNOS mRNA表达水平。结果显示:SAMP8老年组与青年组相比,额叶皮质中nNOS阳性神经元的数量显著增加(15.8±6.3vs8.0±4.9,P<0.05);SAMP8与SAMR1比较,青年组额叶皮质nNOS阳性神经元的数量差异无统计学意义,老年组额叶皮质nNOS阳性神经元的数量显著增加(15.8±6.3vs7.5±5.3,P<0.05)。SAMP8老年组额叶皮质nNOS mRNA水平明显高于SAMP8青年组(1.00±0.17vs0.67±0.13,P<0.01)和老年组SAMR1(1.00±0.17vs0.67±0.11,P<0.01)。以上结果提示:额叶皮质中nNOS神经元的数量增加可能产生过量NO,NO可能参与了SAMP8快速衰老的过程。本研究的结果为通过调节额叶皮质NO产量来延缓衰老及衰老相关功能障碍提供了依据。
To observe age-related changes of the neuronal type of the nitric oxide synthase （nNOS） in frontal cortex in the senescence ac- celerated mouse （SAM）, and to investigate the role of nNOS in the aging of central nervous system（CNS）. Senescence accelerated mouse/prone 8 （ SAMP8 ） and senescence accelerated mouse/resistance 1 （ SAMR1 ） were enrolled into the experimental group and control group, respectively. The animals in both groups were further subdivided into young group （2 months） and aged group （ 10 months）. The distribution and number of nNOS positive neurons and nNOS mRNA levels in frontal cortex were detected by immunohistochemical analysis and RT-PCR analysis, respectively. The results indicated that the number of nNOS immunoreactive neurons increased in frontal cortex （ 15. 8±6.3 vs 8.0 ± 4.9, P 〈 0.05 ） of aged SAMP8 compared to young SAMP8. Compared with age matched SAMR1, aged SAMP8 had more nNOS immunoreactive neurons in frontal cortex （ 15.8 ± 6.3 vs 7.5 ± 5.3, P 〈 0.05 ） and no significant difference was found between young SAMP8 and SAMR1. The expression of nNOS mRNA increased in the frontal cortex of SAMP8 in an age-dependent manner （ old ： 1.00 ± 0.17 vs young： 0.67 ± 0.13, P 〈 0.01 ） and significantly higher levels of nNOS mRNA in the frontal cortex were observedin old SAMP8 as compared to age-matched controls （ 1.00 ±0.17 vs O. 67 ±0.11, P 〈0.01 ）. The present results indicate that there are upregulations of nNOS expression which might result in more production of NO in frontal cortex of aged SAMP8. In these mice, no may contribute to the mechanisms underlying the accelerated ageing processes. These results further provide evidence for that the regulation of NO production in frontal cortex might be used to delay age-related disorders.
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2007年第5期521-525,共5页
Chinese Journal of Neuroanatomy
基金
河北省科技攻关计划项目(062761820)资助项目
关键词
一氧化氮
神经元型一氧化氮合酶
衰老
快速衰老小鼠
额叶皮质
nitric oxide （ NO）, neuronal nitric oxide synthase （nNOS） , aging, senescence accelerated mouse （SAM） , frontal cortex
