Exacerbation of apoptosis in the dentate gyrus of the aged rat by dexamethasone and the protective role of corticosterone

Exacerbation of apoptosis in the dentate gyrus of the aged rat by dexamethasone and the protective role of corticosterone
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DOI:
10.1006/exnr.1996.0113
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发表时间:
1996-07-01
影响因子:
5.3
通讯作者:
Almeida, OFX
Almeida, OFX
中科院分区:
医学2区
文献类型:
--
作者:
Hassan, AHS;vonRosenstiel, P;Almeida, OFX

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使用TUNEL程序检测凋亡细胞,研究了糖皮质激素诱导的不同年龄大鼠齿状回的细胞损失。 1-36月龄大鼠单次注射地塞米松(DEX)后24小时内,观察到齿状门和颗粒细胞层细胞凋亡发生率显着增加;随着年龄的增长,DEX 诱导的细胞凋亡更加明显。皮质酮 (CORT) 不会导致细胞凋亡率增加至高于年龄匹配对照的水平。然而,CORT 预处理(3 小时)导致齿状回两个区域中 DEX 诱导的细胞凋亡显着减弱。经盐水处理的大鼠的血清 CORT 水平在 6 月龄时达到峰值,并在 36 月龄时达到最低点。结果表明,(i)老年受试者更容易受到 DEX 的影响,因为齿状回细胞因凋亡而丢失,()CORT 以高亲和力与 I 型皮质类固醇受体结合,可能有助于防止 DEX 的破坏作用,DEX 是 II 型糖皮质激素受体的配体,(iii) CORT 内源水平的下降可能会增加老年大鼠齿状回对 DEX 损伤的脆弱性。 (C) 1996 学术出版社
Glucocorticoid-induced cell loss in the dentate gyrus of rats of various ages was studied using the TUNEL procedure to detect apoptotic cells. A highly significant increase in the incidence of apoptosis was observed within the dentate hilus and granule cell layer within 24 h of a single injection of dexamethasone (DEX) in rats aged between 1 and 36 months; DEX-induced apoptosis was more pronounced with increasing age. Corticosterone (CORT) did not cause an increase in the rate of apoptosis above that found in age-matched controls. However, CORT pretreatment (3 h) resulted in a significantly attenuated DEX-induced apoptosis in both areas of the dentate gyrus. Serum CORT levels in saline-treated rats peaked at 6 months of age and reached a nadir at 36 months of age. The results indicate that (i) aged subjects are more susceptible to DEX in terms of dentate gyrus cell loss by apoptosis, () CORT, which binds to Type I corticosteroid receptors with a high affinity, might serve to protect against the damaging effects of DEX which is a ligand of the Type II glucocorticoid receptor, and (iii) declining endogenous levels of CORT may increase the vulnerability of the dentate gyrus of aged rats to insult by DEX. (C) 1996 Academic Press, Inc.