Chronic Restraint Stress in Adolescence Differentially Influences Hypothalamic-Pituitary-Adrenal Axis Function and Adult Hippocampal Neurogenesis in Male and Female Rats
Chronic Restraint Stress in Adolescence Differentially Influences Hypothalamic-Pituitary-Adrenal Axis Function and Adult Hippocampal Neurogenesis in Male and Female Rats
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DOI：
10.1002/hipo.20829
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发表时间：
2011-11-01
期刊：
影响因子：
3.5
通讯作者：
Galea, Liisa A. M.
中科院分区：
文献类型：
--
作者：
Barha, Cindy K.;Brummelte, Susanne;Galea, Liisa A. M.
以前的研究表明，青春期的逆境与成年后的健康状况之间存在着性别特异性的关系。青春期的特点是大脑中对压力反应的区域发生了重大变化，包括海马体，海马体是整个生命周期中持续神经发生的部位。与成年大鼠相比，青春期前的雄性和雌性大鼠对慢性应激表现出不同的急性反应，但对这些应激诱导的变化是否持续到成年知之甚少。因此，在这项研究中，我们调查了慢性间歇性应激在青春期基础皮质酮水平，齿状回（DG）的体积，和成年雄性和雌性SD大鼠海马神经发生的影响。从出生后第30-52天（PD）开始，在不可预测的时间，将青春期雄性和雌性大鼠每隔一天束缚1小时，持续3周，或不受干扰。所有大鼠在PD 70成年期接受单次注射溴脱氧尿苷（BrdU; 200 mg/kg），并在3周后灌注。针对Ki 67（细胞增殖的内源性标志物）和BrdU（以估计对细胞存活的影响）处理脑。此外，在束缚应激期和成年期采集血样。结果表明，男性和女性在青春期表现出不同的皮质酮慢性应激反应，只有成年雌性大鼠暴露在青春期的压力表现出较高的基础皮质酮水平相比，nonstressed控制。此外，强调女性表现出减少数量的增殖和存活的细胞在DG在成年期相比，nonstressed同性控制。大多数BrdU标记的细胞与成熟神经元的内源性标记物NeuN共标记，表明在青春期经历慢性束缚应激的成年雌性大鼠DG中神经发生减少。虽然雄性大鼠更敏感的慢性应激表现出较高的皮质酮水平和降低体重的青少年，作为成年人，他们表现出轻微的细胞存活率增加，青春期应激对基础皮质酮水平没有影响。这些结果表明，在青春期的压力可以影响下丘脑-垂体-肾上腺轴功能和海马可塑性在成年期，特别是在雌性大鼠。(c)2010 Wiley Periodicals，Inc.
Previous studies have shown a relationship between adversity in adolescence and health outcomes in adulthood in a sex-specific manner. Adolescence is characterized by major changes in stress-responsive regions of the brain, including the hippocampus, the site of ongoing neurogenesis throughout the lifespan. Prepubertal male and female rats exhibit different acute reactions to chronic stress compared to adults, but less is known about whether these stress-induced changes persist into adulthood. Therefore, in this study, we investigated the effects of chronic, intermittent stress during adolescence on basal corticosterone levels, dentate gyrus (DG) volume, and neurogenesis in the hippocampus of adult male and female Sprague-Dawley rats. Adolescent male and female rats were either restrained for 1 h every other day for 3 weeks from postnatal days (PDs) 30-52 at unpredictable times or left undisturbed. All rats received a single injection of bromodeoxyuridine (BrdU; 200 mg/kg) in adulthood on PD70 and were perfused 3 weeks later. Brains were processed for Ki67 (endogenous marker of cell proliferation) and BrdU (to estimate effects on cell survival). In addition, blood samples were taken during the restraint stress period and in adulthood. Results show that males and females exhibit different corticosterone responses to chronic stress during adolescence and that only adult female rats exposed to stress during adolescence show higher basal corticosterone levels compared to nonstressed controls. Furthermore, stressed females showed a reduced number of proliferating and surviving cells in the DG in adulthood compared to nonstressed same-sex controls. The majority of BrdU-labeled cells were co-labeled with NeuN, an endogenous marker of mature neurons, indicating that neurogenesis was decreased in the DG of adult female rats that had undergone chronic restraint stress in adolescence. Although male rats were more responsive to the chronic stress as adolescents showing higher corticosterone levels and reduced body weight, as adults they showed a slight increase in cell survival and no effect of adolescent stress on basal corticosterone levels. These results suggest that stress during adolescence can have effects on hypothalamic-pituitary-adrenal axis function and hippocampus plasticity in adulthood, particularly in female rats. (c) 2010 Wiley Periodicals, Inc.