Department of Neurobiology, University of Haifa, Mount Carmel, Haifa, Israel.
Stress. 2012 Jul;15(4):416-24. doi: 10.3109/10253890.2011.634036. Epub 2011 Dec 21.
During the juvenile period rodents are particularly sensitive to stressors. Aversive events encountered during this period may have enduring effects that are not evident among animals initially stressed as adults. Interestingly, experiencing stressor during juvenile period was found to elicit a biphasic behavioral pattern over the course of development. During the juvenile period, the expression of several GABAA receptor subunits is subject to elevated plasticity, rendering the GABAergic system sensitive to stressors. In the present investigation, animals were exposed to a juvenile variable stressor regimen (JUV-S) at 27-29 postnatal days (PND): 27 PND-acute swim stress (10 min), 28 PND-elevated platform stress (3 sessions×30 min each), and 29 PND-restraint (2 h). One hour following the last exposure to stressor or in adulthood (60 PND), anxiety-related behaviors were assessed in a 5-min elevated plus maze test. The western blotting technique was used to evaluate whether the juvenile stress induced behavioral pattern will be accompanied by respective changes in GABAA α1, α2, and α3 protein expression in male rats. Our findings further established that juvenile stressor elicits hyper-reactivity when rats were tested as juveniles, whereas rats exhibited reduced activity and increased anxiety when tested as adults. Additionally, the effects of juvenile stressor on α1, α2, and α3 were more pronounced among juvenile stressed rats that were challenged as adults compared with rats that were only challenged as juveniles. Interestingly, the stress-induced modulation of the subunits was particularly evident in the amygdala, a brain region closely associated with anxiety. Thus, age- and region-specific alterations of the α subunits may contribute to the age-specific behavioral alterations observed following juvenile stress exposure.
在幼年时期，啮齿动物对压力特别敏感。在这个时期遇到的不愉快事件可能会产生持久的影响，而在最初作为成年人受到压力的动物中并不明显。有趣的是，研究发现，在幼年时期经历压力源会在发育过程中引发双相行为模式。在幼年时期，几种 GABA A 受体亚基的表达受到高度可塑性的影响，使 GABA 能系统对压力源敏感。在本研究中，动物在 27-29 日龄（PND）时接受了一种幼年可变应激方案（JUV-S）：27 PND-急性游泳应激（10 分钟）、28 PND-高架平台应激（3 次×30 分钟）和 29 PND-束缚（2 小时）。在最后一次暴露于应激源或成年后（60 PND）1 小时，在 5 分钟高架十字迷宫测试中评估焦虑相关行为。Western 印迹技术用于评估幼年应激是否会伴随着雄性大鼠 GABA A α1、α2 和 α3 蛋白表达的相应变化。我们的研究结果进一步证实，幼年应激源会在大鼠作为幼年动物进行测试时引起过度反应，而当大鼠作为成年动物进行测试时，它们表现出活动减少和焦虑增加。此外，与仅作为幼年动物受到挑战的大鼠相比，作为成年动物受到挑战的幼年应激大鼠的应激源对 α1、α2 和 α3 的影响更为明显。有趣的是，应激诱导的亚基调节在杏仁核中更为明显，杏仁核是与焦虑密切相关的脑区。因此，α 亚基的年龄和区域特异性改变可能导致幼年应激暴露后观察到的年龄特异性行为改变。
