Differential effects of corticosterone and dexamethasone on hippocampal neurogenesis in vitro.

Differential effects of corticosterone and dexamethasone on hippocampal neurogenesis in vitro.
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DOI:
10.1016/j.bbrc.2004.03.071
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发表时间:
2004-04
影响因子:
3.1
通讯作者:
In Tag Yu;Sang-Hun Lee;Yong-Sung Lee;H. Son
In Tag Yu;Sang-Hun Lee;Yong-Sung Lee;H. Son
中科院分区:
生物学4区
文献类型:
--
作者:
In Tag Yu;Sang-Hun Lee;Yong-Sung Lee;H. Son

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胎儿发育期间的产前应激导致成年后齿状回神经发生的阻滞。本研究旨在探讨糖皮质激素受体在皮质酮对胎儿海马前体细胞神经发生作用中的主导作用。为此,皮质酮和地塞米松影响的关键分子的表达进行了比较在海马祖细胞的增殖和分化。皮质酮(2μM)使溴脱氧尿苷标记的细胞数量显著减少(约50%),并引起微管相关蛋白2标记的细胞树突萎缩。皮质酮可显著降低脑缺血再灌注损伤后神经元D、BDNF和NR 1的mRNA表达水平及p-ERK和p-CREB的蛋白表达水平,并呈剂量依赖性。与此相反,地塞米松,糖皮质激素受体(GR)特异性激动剂,有增殖抑制作用,但不分化。它的结论是,皮质酮elizes其对神经发生,包括增殖和分化的影响,而糖皮质激素受体的刺激是足以减少只有增殖。
Prenatal stress during fetal development results in the blockade of neurogenesis in the dentate gyrus in adulthood. Present study was undertaken to investigate the dominant role of the glucocorticoid receptors in corticosterone actions on the neurogenesis of fetal hippocampal progenitor cells. For that purpose, expressions of key molecules affected by corticosterone and dexamethasone were compared during proliferation and differentiation of the hippocampal progenitor cells. Corticosterone (2μM) significantly decreased the number of bromodeoxyuridine-labeled cells (about 50%) and caused the dendritic atrophy in microtubule-associated protein 2-labeled cells. The expressions of NeuroD, BDNF, and NR1 mRNA levels and protein levels of p-ERK and p-CREB were remarkably decreased by corticosterone in a dose-dependent manner. In contrast, dexamethasone, a glucocorticoid receptor (GR) specific agonist, had an inhibitory effect on proliferation, but not differentiation. It is concluded that corticosterone elicits its effects on neurogenesis including proliferation and differentiation whereas stimulation of the glucocorticoid receptor is sufficient to decrease only proliferation.