类固醇受体辅助活化因子-1在成年与老年雌性大鼠脑内的表达研究

Expression of steroid receptor coactivator-1 in the brain of adult and aged female rats

目的研究雌性大鼠脑老化过程中脑内类固醇受体辅助活化因子(SRC-1)表达的变化。方法硫酸镍铵增强显色的免疫组化SP法。结果SRC-1免疫阳性产物广泛分布于脑内,免疫阳性产物主要位于细胞核,但是在个别主要与运动有关的核团则明显位于细胞胞膜或胞浆。在成年,最高表达见于大脑皮质大部、海马、桥核、前嗅核、网状外侧核、小脑蒲肯野细胞等部位;中等强度的表达见于隔区、丘脑和脑干,较低水平的表达见于某些下丘脑和脑干的核团。和成年的表达水平相比,老年大鼠的前嗅核、斜角带垂直部、基底神经节、杏仁皮质后核、黑质、脑桥、网状外侧核和小脑浦肯野细胞等部位的表达显著下降,但是在大脑皮质、下丘脑和丘脑以及脑干的很多部位基本保持不变,在极个别核团甚至有所上升。结论SRC-1在大鼠脑内的表达比较广泛,可能参与了对多种重要脑功能的调节;老年脑内主要与运动调控和学习记忆有关脑区内SRC-1表达的降低提示SRC-1可能在脑老化导致的学习记忆障碍以及帕金森综合征等神经退行性疾病中有重要意义。核外SRC-1主要见于与运动有关的核团,提示SRC-1有可能通过第二信使途径发挥对运动功能的快速调节。

Objective To examine the expression of steroid receptor coactivator-1（SRC-1） in the adult and aged female rat brain.Methods Nickel-intensified immunohistochemistry was used to identify the expression of SRC-1.Results SRC-1 immunoreactivities were extensively distributed in the brain,while most of the immunopositive materials were localized in the cell nuclei;surprisingly they were also detected in the extra-nuclear components.High levels of SRC-1 immunoreactivities were detected in the olfatory bulb,most of the cerebral cortex,hippocampus,pontine nuclei,lateral reticular nucleus,and cerebellar Purkinje cells;moderate levels were detected in some areas of the septal area,thalamus and brain stem;lower expression was detected in some nuclei of the hypothalamus and brain stem.Striking age-related decrease of SRC-1 expression was noticed in the olfactory nucleus,basal ganglion,substantia nigra,pontine nucleus,lateral reticular nucleus as well as Purkinje cells.Conclusions The above data suggested multifunctional roles of SRC-1 in the brain.The age-related decrease of SRC-1 in some specific nuclei strongly suggested its potential roles in the regulation of cholinergic and dopaminergic neurons,which may be one of the underlying mechanisms of the vulnerability of the aged brain.Additionally,the extra-nucleus SRC-1 implied it may also function through a novel non-genomic signaling pathway in the brain.