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早期与晚期母体剥夺对压力的内分泌和下丘脑反应有不同影响。

Early vs. late maternal deprivation differentially alters the endocrine and hypothalamic responses to stress.

作者信息

van Oers H J, de Kloet E R, Levine S

机构信息

Department of Psychology, University of Delaware, Newark, DE 19716-2577, USA.

出版信息

Brain Res Dev Brain Res. 1998 Dec 7;111(2):245-52. doi: 10.1016/s0165-3806(98)00143-6.

Abstract

Twenty-four hours of maternal deprivation results in persistent changes in the ACTH response to mild stress. These effects are dependent on the age of the neonate at the time of deprivation. Pups that were separated from the dam at postnatal days (pnd) 3-4 showed an enhanced stress-induced ACTH response at age 20, while pups deprived at pnd 11-12 displayed an attenuated ACTH response to stress at that time. The present study was designed to test the hypothesis that the immediate effects of deprivation at pnd 3 vs. pnd 11 would provide an explanation for these paradoxical effects observed at day 20. For this purpose, we measured the basal and the stress-induced ACTH and corticosterone (CORT) response at days 4 and 12, following 24 h of maternal deprivation. Furthermore, we examined whether similar differences in c-fos and CRH mRNA expression in the paraventricular nucleus (PVN) accompanied the differences in response characteristics of ACTH at pnd 20. The results indicate that changes in the ACTH and CORT responses were minimal after 24 h of maternal deprivation at day 4, whereas these hormones were markedly elevated following deprivation at day 12. The persistent effects also showed age-dependency: pups deprived early showed at pnd 20 an exaggerated ACTH response. Late deprived juveniles exhibited an attenuated ACTH response to stress at pnd 20 while in both conditions the CORT response was not different from the non-deprived litter mates. These persistent endocrine changes were accompanied by the changes in the neural stress markers. The expressions of c-fos and CRH mRNA in the PVN were at pnd 20 significantly greater in their controls in early-deprived animals. The late deprived juveniles showed a reduced response in these neural markers. In conclusion, the persistent alterations in ACTH are reflected by changes in c-fos and CRH mRNA, but these changes in endocrine and in neural stress markers do not appear to be related to any of the hormonal changes that occur at the time of maternal deprivation.

摘要

24小时的母婴分离会导致促肾上腺皮质激素(ACTH)对轻度应激的反应持续改变。这些影响取决于新生儿在分离时的年龄。在出生后第3 - 4天(pnd)与母鼠分离的幼崽在20日龄时表现出应激诱导的ACTH反应增强,而在pnd 11 - 12时分离的幼崽在那时对应激的ACTH反应减弱。本研究旨在检验以下假设:在pnd 3与pnd 11时分离的即时效应能够解释在20日龄时观察到的这些矛盾效应。为此,我们在母婴分离24小时后的第4天和第12天测量了基础状态以及应激诱导的ACTH和皮质酮(CORT)反应。此外,我们检查了在pnd 20时,室旁核(PVN)中c - fos和促肾上腺皮质激素释放激素(CRH)mRNA表达的类似差异是否伴随着ACTH反应特征的差异。结果表明,在第4天母婴分离24小时后,ACTH和CORT反应的变化最小,而在第12天分离后这些激素显著升高。持续效应也显示出年龄依赖性:早期分离的幼崽在pnd 20时表现出夸张的ACTH反应。晚期分离的幼崽在pnd 20时对应激的ACTH反应减弱,而在两种情况下,CORT反应与未分离的同窝幼崽没有差异。这些持续的内分泌变化伴随着神经应激标志物的变化。在pnd 20时,早期分离动物的PVN中c - fos和CRH mRNA的表达在其对照组中显著更高。晚期分离的幼崽在这些神经标志物上表现出反应降低。总之,ACTH的持续改变反映在c - fos和CRH mRNA的变化中,但这些内分泌和神经应激标志物的变化似乎与母婴分离时发生的任何激素变化无关。

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