Gould E, Cameron H A, Daniels D C, Woolley C S, McEwen B S
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.
J Neurosci. 1992 Sep;12(9):3642-50. doi: 10.1523/JNEUROSCI.12-09-03642.1992.
The rat dentate gyrus is unusual among mammalian brain regions in that it shows cell birth well into adulthood. During development, dentate gyrus cell birth is regulated by adrenal steroids. However, it is presently unknown whether cell division in the adult is also mediated by these same factors. In order to determine whether this is the case, we combined adrenalectomy, with or without corticosterone (CORT) replacement, and 3H-thymidine autoradiography, Nissl staining, and immunohistochemistry for the glial cell markers vimentin and glial fibrillary acidic protein (GFAP) as well as for the neuronal marker neuron-specific enolase. Removal of circulating adrenal steroids resulted in a greater density of both GFAP-immunoreactive and vimentin-immunoreactive cells compared to sham-operated animals; CORT replacement prevented increases in both of these cell types. The increase in the density of vimentin-immunoreactive cells probably resulted from an increase in the birth of these cells, as adrenalectomized rats showed greater numbers of 3H-thymidine-labeled vimentin-positive cells compared to sham rats. In contrast, no changes in the number of 3H-thymidine-labeled GFAP-positive cells were observed with adrenalectomy, indicating that the increase in this cell type probably does not involve cell birth. In addition, the density of 3H-thymidine-labeled cells that were not immunoreactive for either glial cell marker and that showed neuronal characteristics was dramatically increased with adrenalectomy. These results suggest that adrenal hormones normally suppress the birth of both glia and neurons in the adult rat dentate gyrus.
大鼠齿状回在哺乳动物脑区中较为特殊,因为它在成年后仍有细胞生成。在发育过程中,齿状回的细胞生成受肾上腺类固醇调节。然而,目前尚不清楚成年期的细胞分裂是否也由这些相同因素介导。为了确定是否如此,我们将肾上腺切除术(有无皮质酮(CORT)替代)与³H-胸腺嘧啶核苷放射自显影、尼氏染色以及针对胶质细胞标志物波形蛋白和胶质纤维酸性蛋白(GFAP)以及神经元标志物神经元特异性烯醇化酶的免疫组织化学相结合。与假手术动物相比,去除循环中的肾上腺类固醇导致GFAP免疫反应性细胞和波形蛋白免疫反应性细胞的密度更高;CORT替代可防止这两种细胞类型的增加。波形蛋白免疫反应性细胞密度的增加可能是由于这些细胞生成的增加,因为与假手术大鼠相比,肾上腺切除大鼠显示出更多³H-胸腺嘧啶核苷标记的波形蛋白阳性细胞。相反,肾上腺切除术后未观察到³H-胸腺嘧啶核苷标记的GFAP阳性细胞数量的变化,表明这种细胞类型的增加可能不涉及细胞生成。此外,肾上腺切除术后,对两种胶质细胞标志物均无免疫反应且具有神经元特征的³H-胸腺嘧啶核苷标记细胞的密度显著增加。这些结果表明,肾上腺激素通常会抑制成年大鼠齿状回中胶质细胞和神经元的生成。