Sugaya K, Chouinard M, Greene R, Robbins M, Personett D, Kent C, Gallagher M, McKinney M
Department of Pharmacology, Mayo Clinic Jacksonville, Florida 32224, USA.
J Neurosci. 1996 May 15;16(10):3427-43. doi: 10.1523/JNEUROSCI.16-10-03427.1996.
Spatial learning ability was quantitated in young and aged Long-Evans rats, and molecular markers were assessed in the striatum and hippocampal formation using immunocytochemical, immunoblotting, and in situ hybridization histochemical procedures. The mRNA for beta-amyloid precursor protein (beta APP), most likely the transcript encoding the 695-amino acid form of this protein, was elevated in pyramidal and granule cells in the hippocampus of aged rats exhibiting poorer spatial learning. In immunoblots of hippocampal protein extracts, however, the level of beta APP-like immunoreactivity was depressed in the more impaired subjects. Similarly, the level in hippocampus of the mRNA for manganese-dependent superoxide dismutase (Mn-SOD), a marker of oxidative stress, was positively correlated with the degree of behavioral impairment, but immunoblotting revealed that Mn-SOD protein was depressed in the aged hippocampus compared with young. The mRNAs for the neuronal form of nitric oxide synthase and for the astrocyte marker glial fibrillary acidic protein (GFAP) were elevated in the hippocampus in correlation with the extent of learning impairment. In the striatum, the levels of mRNA and protein for several candidate genes, including GFAP, were elevated in parallel with the learning index, but these were age effects. Several hippocampal proteins were unchanged (GFAP) or depressed (beta APP and Mn-SOD) in level, despite elevations in corresponding mRNAs. In the aged cohort, hippocampal GFAP mRNA, Mn-SOD mRNA, and beta APP emerged as predictors of behavioral impairment, suggesting the involvement of these hippocampal systems in age-related cognitive impairment.
在年轻和老年Long-Evans大鼠中对空间学习能力进行了定量分析，并使用免疫细胞化学、免疫印迹和原位杂交组织化学方法在纹状体和海马结构中评估了分子标记物。在空间学习能力较差的老年大鼠海马的锥体细胞和颗粒细胞中，β-淀粉样前体蛋白（β-APP）的mRNA水平升高，该mRNA很可能编码这种蛋白的695个氨基酸形式的转录本。然而，在海马蛋白提取物的免疫印迹中，β-APP样免疫反应性水平在损伤更严重的大鼠中降低。同样，氧化应激标志物锰依赖性超氧化物歧化酶（Mn-SOD）的mRNA在海马中的水平与行为损伤程度呈正相关，但免疫印迹显示，与年轻大鼠相比，老年大鼠海马中的Mn-SOD蛋白水平降低。神经元型一氧化氮合酶和星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）的mRNA在海马中的水平升高，与学习损伤程度相关。在纹状体中，包括GFAP在内的几种候选基因的mRNA和蛋白水平与学习指数平行升高，但这些是年龄效应。尽管相应的mRNA水平升高，但几种海马蛋白的水平未发生变化（GFAP）或降低（β-APP和Mn-SOD）。在老年组中，海马GFAP mRNA、Mn-SOD mRNA和β-APP成为行为损伤的预测指标，表明这些海马系统参与了与年龄相关的认知损伤。
