Desjardins S, Mayo W, Vallée M, Hancock D, Le Moal M, Simon H, Abrous D N
INSERM U-259, Université Bordeaux II, France.
Neurobiol Aging. 1997 Jan-Feb;18(1):37-44. doi: 10.1016/s0197-4580(96)00206-0.
In the present study the effect of aging on the basal expression of three different immediate early genes (IEGs) was investigated. The protein products of c-fos, c-jun, and egr-1 genes were visualized immunohistochemically in the rat hippocampus of young adult (4-month-old) and old rats (20-month-old). Astrocytes were quantified by GFAp immunostaining to determine whether changes in the expression of IEGs were correlated with modifications in this marker of degenerative changes. In the young adult rat brain, basal levels of c-Jun and Egr-1 but not c-Fos were detected within the hippocampal formation. Whereas very high basal levels of c-Jun were found in the dentate granule cells and in the pyramidal cells of the ventral hippocampus, Egr-1 was highly expressed in the CA1 pyramidal cells of the dorsal hippocampus. Aging was accompanied by a decrease in Egr-1 expression, by a decrease in total cell density, as well as by a loss of astrocytes in CA1 subfields. In contrast, basal expression of c-Fos and c-Jun as well as astrocyte density within the dentate gyrus were not affected by aging. No difference in these markers was observed in aged rats with or without impairment in spatial learning in a water maze. It was concluded that although these changes may reflect senescence-induced decline of brain function, they do not constitute the defect underlying the age-associated reduction in mnesic capability.
在本研究中，研究了衰老对三种不同即刻早期基因（IEGs）基础表达的影响。采用免疫组织化学方法，在年轻成年（4月龄）和老年大鼠（20月龄）的海马中观察c-fos、c-jun和egr-1基因的蛋白质产物。通过胶质纤维酸性蛋白（GFAp）免疫染色对星形胶质细胞进行定量，以确定IEGs表达的变化是否与这种退行性变化标志物的改变相关。在年轻成年大鼠脑中，海马结构内可检测到c-Jun和Egr-1的基础水平，但未检测到c-Fos的基础水平。在齿状颗粒细胞和腹侧海马的锥体细胞中发现c-Jun的基础水平非常高，而Egr-1在背侧海马的CA1锥体细胞中高表达。衰老伴随着Egr-1表达的降低、总细胞密度的降低以及CA1亚区星形胶质细胞的丢失。相比之下，齿状回内c-Fos和c-Jun的基础表达以及星形胶质细胞密度不受衰老影响。在水迷宫中空间学习有无损伤的老年大鼠中，这些标志物均未观察到差异。得出的结论是，尽管这些变化可能反映了衰老诱导的脑功能衰退，但它们并不构成与年龄相关的记忆能力下降的潜在缺陷。
