Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid levels
Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid levels
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DOI：
10.1002/hipo.20074
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Bender, RA
中科院分区：
文献类型：
--
作者：
Brunson, KL;Baram, TZ;Bender, RA
一般认为齿状回颗粒细胞的神经发生受糖皮质激素的负调控。我们检验了一种假设，即从出生后早期开始暴露于低血浆皮质类固醇水平，可以提高成年期颗粒细胞的增殖率。大鼠幼鼠在出生后第10天切除肾上腺（ADX），然后通过口服补充低皮质酮水平“夹住”一生。与年龄匹配的假手术对照组相比，在3个月和12个月时，用BrdU免疫化学测定夹钳大鼠的神经发生。在3个月和12个月时，两组之间的神经发生率没有差异。与3个月大的大鼠相比，12个月大的大鼠明显更低，尽管只有在假adx大鼠中存在血浆皮质酮的年龄依赖性增加。在两组中，颗粒细胞层体积、颗粒细胞密度和颗粒细胞变性（用凋亡标志物测定）没有区别，进一步支持了不同慢性糖皮质激素水平下神经发生率的可变性。此外，成年大鼠急性血浆糖皮质激素剥夺（肾上腺切除术）引起颗粒细胞神经发生爆发，而成年大鼠完全消除这些激素（通过停止激素补充），早期生活的ADX/夹住没有。这些数据不支持慢性血浆糖皮质激素水平与颗粒细胞神经发生之间的简单反比关系。具体来说，在生命早期开始的糖皮质激素水平的慢性调节会引发额外的、适应性的和代偿机制，这些机制有助于调节颗粒细胞的增殖。(c) 2005 Wiley-Liss, Inc。
Neurogenesis of dentate gyrus granule cells is generally considered to be negatively regulated by glucocorticoids. We tested the hypothesis that exposure to low plasma corticosteroid levels starting in the early postnatal period enhances granule cell proliferation rate during adulthood. Rat pups were adrenalectomized (ADX) on postnatal day 10 and were then "clamped" throughout life at low corticosterone levels via oral supplementation. Neurogenesis was determined using BrdU immunochemistry at 3 and 12 months in clamped rats as compared with age-matched, sham-operated controls. Rate of neurogenesis did not differ between the groups at either 3 or 12 months. It was significantly lower in 12-month-old compared with 3-month-old rats, despite the presence of an age-dependent increase of plasma corticosterone only in the sham-ADX rats. Granule cell layer volume, granule cell density, and granule cell degeneration (determined using apoptotic markers) were indistinguishable in the two groups, further supporting the comparable rate of neurogenesis under differing chronic glucocorticoid levels. In addition, whereas acute deprivation of plasma glucocorticoids (adrenalectomy) in adult rats evoked a burst of granule cell neurogenesis, complete elimination of these hormones (by stopping hormone supplementation) in adult, early-life ADX/clamped rats did not. These data do not support a simple inverse relationship between chronic plasma glucocorticoid levels and granule cell neurogenesis. Specifically, chronic modulation of glucocorticoid levels commencing early in life evokes additional, adaptive, and compensatory mechanisms that contribute to the regulation of granule cell proliferation. (c) 2005 Wiley-Liss, Inc.