CHRONIC HIGH CORTICOSTERONE REDUCES NEUROGENESIS IN THE DENTATE GYRUS OF ADULT MALE AND FEMALE RATS
CHRONIC HIGH CORTICOSTERONE REDUCES NEUROGENESIS IN THE DENTATE GYRUS OF ADULT MALE AND FEMALE RATS
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DOI：
10.1016/j.neuroscience.2010.04.023
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发表时间：
2010-07-14
期刊：
影响因子：
3.3
通讯作者：
Galea, L. A. M.
中科院分区：
文献类型：
--
作者：
Brummelte, S.;Galea, L. A. M.
海马齿状回的成人神经发生随着应激暴露而改变，并与抑郁症有关。高水平皮质酮（CORT）抑制雄性大鼠齿状回的神经发生。然而，急性和慢性应激均不一致地减少雌性大鼠成年海马神经发生。因此，本研究旨在探讨不同剂量皮质酮对雌雄大鼠海马神经发生的影响。给大鼠注射10或40 mg/kg CORT精油21天。最后一次注射CORT后24小时灌注，分析脑内细胞增殖（ki67标记）或未成熟神经元（双皮质素标记）。结果表明，在雄性和雌性小鼠中，高CORT均降低了齿状回细胞的增殖和未成熟神经元的密度，而低CORT则没有。此外，高CORT的雄性海马腹侧和背侧未成熟神经元密度均降低，而高CORT的雌性海马仅显示腹侧海马未成熟神经元密度降低。高剂量的CORT扰乱了雌性的发情周期。此外，低剂量的CORT显著降低了男性的体重增加，增加了基础CORT水平，但女性没有，这表明低剂量CORT的男性更容易受到伤害。因此，我们发现慢性皮质激素对体重和背齿状回神经发生的反应存在微妙的性别差异，这可能在理解不同性别对压力相关神经精神疾病的不同脆弱性方面发挥作用。(c) 2010 ibro。Elsevier Ltd.出版。版权所有。
Adult neurogenesis in the dentate gyrus of the hippocampus is altered with stress exposure and has been implicated in depression. High levels of corticosterone (CORT) suppress neurogenesis in the dentate gyrus of male rats. However both acute and chronic stress do not consistently reduce adult hippocampal neurogenesis in female rats. Therefore, this study was conducted to investigate the effect of different doses of corticosterone on hippocampal neurogenesis in male and female rats. Rats received 21 days of s.c. injections of either oil, 10 or 40 mg/kg CORT. Subjects were perfused 24 h after the last CORT injection and brains were analyzed for cell proliferation (Ki67-labeling) or immature neurons (doublecortin-labeling). Results show that in both males and females high CORT, but not low CORT, reduced both cell proliferation and the density of immature neurons in the dentate gyrus. Furthermore, high CORT males had reduced density in immature neurons in both the ventral and dorsal regions while high CORT females only showed the reduced density of immature neurons in the ventral hippocampus. The high dose of CORT disrupted the estrous cycle of females. Further, the low dose of CORT significantly reduced weight gain and increased basal CORT levels in males but not females, suggesting a greater vulnerability in males with the lower dose of CORT. Thus we find subtle sex differences in the response to chronic CORT on both body weight and on neurogenesis in the dorsal dentate gyrus that may play a role in understanding different vulnerabilities to stress-related neuropsychiatric disorders between the sexes. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.