Lechner S M, Valentino R J
Department of Psychiatry, Allegheny University of the Health Sciences, Broad and Vine Sts., Philadelphia, PA 19102-1192, USA.
Brain Res. 1999 Jan 16;816(1):17-28. doi: 10.1016/s0006-8993(98)00900-7.
The stress-related neurohormone, corticotropin-releasing factor (CRF), also acts as a neurotransmitter to activate the brain noradrenergic nucleus, locus coeruleus (LC). Previous electrophysiological findings demonstrating that tonic CRF secretion in the LC is increased in adrenalectomized rats suggest that activity of certain CRF afferents to the LC is under inhibitory regulation by endogenous corticosteroids. The present study was designed to identify putative CRF afferents to the LC that may be regulated by glucocorticoids. Retrograde tract tracing from the rat LC and pericoerulear regions was combined with immunohistochemistry to visualize CRF and glucocorticoid receptors in the same sections of rat brain. The retrograde tracer, wheat germ agglutinin conjugated to horseradish peroxidase coupled to gold (WGA-Au-HRP) was injected into either the nucleus LC or the rostrolateral pericoerulear region (peri-LC), where CRF-immunoreactive terminals have been demonstrated to synapse with LC dendrites. Sections were processed to visualize the tracer, as well as CRF- and glucocorticoid receptor-immunoreactivity. Following injections of WGA-Au-HRP into the nuclear LC, triple labeled neurons were observed primarily in Barrington's nucleus, where 74+/-4% of retrogradely labeled CRF-immunoreactive neurons colocalized glucocorticoid receptor immunoreactivity. In contrast, injections that incorporated the rostrolateral peri-LC retrogradely labeled numerous neurons that were immunoreactive for both CRF and glucocorticoid receptors in the central nucleus of the amygdala. Thus, 94+/-2% of the retrogradely labeled CRF-immunoreactive neurons in the central nucleus of the amygdala colocalized glucocorticoid receptor immunoreactivity. Additionally, triple labeled neurons were observed in the bed nucleus of the stria terminalis following WGA-Au-HRP injections that incorporated the rostrolateral peri-LC. The present results implicate Barrington's nucleus, the central nucleus of the amygdala and the bed nucleus of the stria terminalis as glucocorticoid-sensitive sources of CRF that can influence the LC-noradrenergic system. Alterations in glucocorticoid levels or glucocorticoid receptor function would be predicted to affect the impact of these specific CRF systems on LC activity.
应激相关神经激素促肾上腺皮质激素释放因子（CRF）也作为一种神经递质来激活脑去甲肾上腺素能核团蓝斑（LC）。先前的电生理学研究结果表明，肾上腺切除的大鼠蓝斑中CRF的持续性分泌增加，这表明某些向蓝斑投射的CRF传入神经的活动受到内源性皮质类固醇的抑制调节。本研究旨在确定可能受糖皮质激素调节的向蓝斑投射的假定CRF传入神经。将来自大鼠蓝斑和蓝斑周围区域的逆行束路追踪与免疫组织化学相结合，以在大鼠脑的同一切片中观察CRF和糖皮质激素受体。将与辣根过氧化物酶偶联的小麦胚凝集素结合金（WGA-Au-HRP）这种逆行示踪剂注射到蓝斑核或蓝斑前外侧周围区域（蓝斑周围区），在该区域已证实有CRF免疫反应性终末与蓝斑树突形成突触。对切片进行处理以观察示踪剂以及CRF和糖皮质激素受体免疫反应性。将WGA-Au-HRP注射到蓝斑核后，主要在巴林顿核中观察到三重标记神经元，其中74±4%的逆行标记的CRF免疫反应性神经元共定位有糖皮质激素受体免疫反应性。相比之下，将示踪剂注射到蓝斑前外侧周围区后进行逆行标记，在杏仁核中央核中有大量对CRF和糖皮质激素受体均有免疫反应性的神经元。因此，杏仁核中央核中94±2%的逆行标记的CRF免疫反应性神经元共定位有糖皮质激素受体免疫反应性。此外，将示踪剂注射到蓝斑前外侧周围区后，在终纹床核中也观察到了三重标记神经元。本研究结果表明，巴林顿核、杏仁核中央核和终纹床核是对糖皮质激素敏感的CRF来源，可影响蓝斑-去甲肾上腺素能系统。预计糖皮质激素水平或糖皮质激素受体功能的改变会影响这些特定CRF系统对蓝斑活动的影响。
