Gould E, Woolley C S, Cameron H A, Daniels D C, McEwen B S
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.
J Comp Neurol. 1991 Nov 15;313(3):486-93. doi: 10.1002/cne.903130309.
Unlike the majority of mammalian brain regions, the rat dentate gyrus undergoes maximal cell birth and cell death during the same developmental time period. Granule cell birth and death peak at the end of the first postnatal week. We have found that manipulations of glucocorticoid levels during the stress hyporesponsive period profoundly influence the density of pyknotic cells in the dentate gyrus while apparently not affecting the density of healthy cells. This raises the possibility that glucocorticoids are regulating processes in addition to cell death, i.e., cell birth. In order to determine whether increases in circulating glucocorticoids or mineralocorticoids affect the birth of cells in the developing dentate gyrus, 3H-thymidine autoradiography was performed on brains of rat pups treated with either corticosterone or aldosterone during the first postnatal week. Quantitative analysis of 3H-thymidine-labelled cells revealed significant decreases in the density of labelled cells in the granule cell layers with both corticosterone and aldosterone treatment. In these same brains, significant decreases in the density of pyknotic cells were also observed in the granule cell layers. However, no changes in the numbers of 3H-thymidine-labelled pyknotic cells were observed with any treatment. Increases in circulating corticosterone or aldosterone resulted in significant increases in the density of both 3H-thymidine-labelled and pyknotic cells in the hilus. These results suggest that dentate gyrus cell birth and cell death are related and that these processes are regulated by adrenal steroids.
与大多数哺乳动物脑区不同,大鼠齿状回在相同的发育时间段内经历最大程度的细胞生成和细胞死亡。颗粒细胞的生成和死亡在出生后第一周结束时达到峰值。我们发现,在应激低反应期对糖皮质激素水平进行调控会深刻影响齿状回中固缩细胞的密度,而显然不会影响健康细胞的密度。这就增加了一种可能性,即糖皮质激素除了调节细胞死亡外,还在调节其他过程,即细胞生成。为了确定循环中的糖皮质激素或盐皮质激素的增加是否会影响发育中齿状回的细胞生成,在出生后第一周对用皮质酮或醛固酮处理的幼鼠脑进行了3H-胸腺嘧啶核苷放射自显影。对3H-胸腺嘧啶核苷标记细胞的定量分析显示,皮质酮和醛固酮处理后颗粒细胞层中标记细胞的密度显著降低。在这些相同的大脑中,颗粒细胞层中固缩细胞的密度也显著降低。然而,任何处理均未观察到3H-胸腺嘧啶核苷标记的固缩细胞数量有变化。循环中皮质酮或醛固酮的增加导致海马区3H-胸腺嘧啶核苷标记细胞和固缩细胞的密度显著增加。这些结果表明,齿状回细胞生成和细胞死亡是相关的,并且这些过程受肾上腺类固醇调节。