Differential Behavioral and Neurobiological Effects of Chronic Corticosterone Treatment in Adolescent and Adult Rats.
Differential Behavioral and Neurobiological Effects of Chronic Corticosterone Treatment in Adolescent and Adult Rats.
复制标题
慢性皮质酮治疗对青春期和成年大鼠的不同行为和神经生物学影响
DOI：
10.3389/fnmol.2017.00025
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Si T
中科院分区：
文献类型：
--
作者：
Li J;Xie X;Li Y;Liu X;Liao X;Su YA;Si T
青春期是压力敏感系统不断成熟的关键时期。虽然与成年人相比，青少年个体显示出更高的压力诱导的激素反应，但尚不清楚慢性压力的行为和神经生物学后果是否以及如何在两个年龄组之间有所不同。在这里，我们解决这个问题，通过研究长期暴露于应激激素，皮质酮（CORT），在青少年和成年动物的影响。雄性Sprague-Dawley（SD）大鼠在青春期（出生后第29-49天（PND））或成年期（PND 71-91天）腹膜内注射CORT（40 mg/kg）或载体21天，然后进行行为测试或处死用于蛋白质印迹分析。尽管两个年龄组的身体和神经内分泌效应相似，但慢性CORT治疗产生了一系列行为和神经生物学效应，但年龄差异显著。虽然CORT治疗的成年动物表现出降低蔗糖偏好，增加焦虑水平和认知障碍，CORT治疗的青春期动物表现出增加蔗糖偏好，降低焦虑水平，增加感觉运动门控功能。这些不同的行为改变伴随着相反的变化，在两个年龄组的脑源性神经营养因子（BDNF）的表达水平，磷酸化的NMDA受体，GluN 1，和PSD-95在大鼠海马的专性亚基。这些结果表明，在青春期长期糖皮质激素暴露产生不同的行为和神经生物学的影响，从那些在成年期，这可能是由于糖皮质激素和正在进行的神经发育过程之间的复杂的相互作用在此期间。
Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29–49) or adulthood (PND 71–91) and then subjected to behavioral testing or sacrifice for western blot analyses. Despite of similar physical and neuroendocrine effects in both age groups, chronic CORT treatment produced a series of behavioral and neurobiological effects with striking age differences. While CORT-treated adult animals exhibited decreased sucrose preference, increased anxiety levels and cognitive impairment, CORT-treated adolescent animals demonstrated increased sucrose preference, decreased anxiety levels, and increased sensorimotor gating functions. These differential behavioral alterations were accompanied by opposite changes in the two age groups in the expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylation of the obligatory subunit of the NMDA receptor, GluN1, and PSD-95 in rat hippocampus. These results suggest that prolonged glucocorticoid exposure during adolescence produces different behavioral and neurobiological effects from those in adulthood, which may be due to the complex interaction between glucocorticoids and the ongoing neurodevelopmental processes during this period.