Sensitivity to glucocorticoid-mediated fast-feedback regulation of the hypothalamic-pituitary-adrenal axis is dependent upon stressor specific neurocircuitry.
Sensitivity to glucocorticoid-mediated fast-feedback regulation of the hypothalamic-pituitary-adrenal axis is dependent upon stressor specific neurocircuitry.
复制标题
对糖皮质激素介导的下丘脑-垂体-肾上腺轴快速反馈调节的敏感性取决于应激源特异性神经回路。
DOI：
10.1016/s0006-8993(00)02405-7
复制
发表时间：
2000
期刊：
影响因子：
2.9
通讯作者：
Plotsky,PM
中科院分区：
文献类型：
--
作者：
Thrivikraman,KV;Nemeroff,CB;Plotsky,PM
Fos蛋白免疫反应性（Fos-IR）被用来确定神经回路可能参与调节下丘脑-垂体-肾上腺（HPA）轴的糖皮质激素介导的快速反馈的敏感性暴露于物理应激，出血，或心理应激，airpuff惊吓大鼠。在这些应激反应中，观察到Fos-IR表达的显著区域性脑差异。具体而言，出血后，核Fos-IR增加孤束核和其他脑干区域已知的调节血流动力学过程，包括视上核，下丘脑室旁核（PVN）的大细胞分裂。相反，在喷气惊吓后，背内侧和外侧下丘脑以及外侧隔的Fos-IR增加。因此，脑干神经回路的激活在出血后占主导地位，而前脑神经回路的激活在喷气惊吓后占主导地位。在其他地区，应激诱导的Fos-IR表达的幅度不同的区域特异性的方式。当应激源暴露之前，管理皮质酮，以达到在应激源后的生理范围内的水平，HPA轴的反应被抑制在响应于喷气惊吓，但不是一个小的或中度出血。最后总结：（1）HPA轴活性的快速反馈介导的抑制严重依赖于应激方式;（2）这种明显的选择性反映在介导这些应激的神经回路的性质差异上。有人建议，糖皮质激素介导的HPA轴的快速反馈调节的中央行动的确定需要评估激活的糖皮质激素受体和细胞内信号级联引起的会聚神经元输入之间的相互作用。
Fos-protein immunoreactivity (Fos-IR) was used to identify neurocircuits potentially participating in the regulation of hypothalamic–pituitary–adrenal (HPA) axis sensitivity to glucocorticoid-mediated fast-feedback in rats exposed to the physical stressor, hemorrhage, or the psychological stressor, airpuff startle. Marked regional brain differences in the Fos-IR expression were observed in response to these stressors. Specifically, after hemorrhage, nuclear Fos-IR increased in the nucleus of the solitary tract and other brainstem regions known to regulate hemodynamic processes including the supraoptic nucleus, and the magnocellular division of hypothalamic paraventricular nucleus (PVN). In contrast, after airpuff startle Fos-IR increased in the dorsomedial and lateral hypothalamus as well as in the lateral septum. Thus, activation of brainstem neurocircuits predominated after hemorrhage whereas activation of forebrain neurocircuits predominated after airpuff startle. In other regions, the magnitude of stressor-induced Fos-IR expression varied in a region-specific manner. When stressor exposure was preceded by administration of corticosterone to achieve levels within the physiological range after stressors, HPA axis responses were suppressed in response to the airpuff startle but not to either a small or moderate hemorrhage. In conclusion: (1) fast-feedback mediated inhibition of HPA axis activity is critically dependent upon stressor modality; (2) this apparent selectivity is reflected by differences in the nature of the neurocircuitry mediating these stressors. It is suggested that determination of the central actions of glucocorticoids in mediating fast-feedback regulation of the HPA axis requires evaluation of the interactions between activated glucocorticoid receptors and intracellular signaling cascades evoked by convergent neuronal input.