Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men
Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men
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DOI：
10.1038/sj.mp.4001250
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发表时间：
2003-01-01
影响因子：
11
通讯作者：
Murphy, HA
中科院分区：
文献类型：
--
作者：
Austin, MC;Janosky, JE;Murphy, HA
大量的临床研究和死后脑研究提供了证据，表明过量的促肾上腺皮质激素释放激素（CRH）分泌和神经传递参与了抑郁症的病理生理，一些研究表明，CRH神经传递的过度活跃延伸到下丘脑以外的几个下丘脑外脑区。本研究的目的是验证一种假设，即诊断为重度抑郁症的自杀受害者的特定脑干区域的CRH水平升高。研究人员对11对自杀抑郁症男性受试者和对照组的脑桥冷冻组织切片进行放射免疫细胞化学处理，切片中含有蓝斑核和中叶尾核，使用抗CRH的一抗血清和I-[125]- igg二抗。通过胶片放射自显像定量测定特定脑桥区域crh免疫反应性（IR）水平对应的光密度。抑郁自杀者蓝斑区CRH-IR水平比对照组高30%，中缝区高39%，尾背中缝区高45%。被盖背核和臂旁核内侧的CRH-IR在两组间无差异。这些发现表明，CRH- ir水平在自杀抑郁症患者含去甲肾上腺素和血清素的脑桥核中特异性升高，从而与CRH神经传递在抑郁症患者下丘脑外脑区升高的假设相一致。
A number of clinical investigations and postmortem brain studies have provided evidence that excessive corticotropin-releasing hormone (CRH) secretion and neurotransmission is involved in the pathophysiology of depressive illness, and several studies have suggested that the hyperactivity in CRH neurotransmission extends beyond the hypothalamus involving several extra-hypothalamic brain regions. The present study was designed to test the hypothesis that CRH levels are increased in specific brainstem regions of suicide victims with a diagnosis of major depression. Frozen tissue sections of the pons containing the locus coeruleus and caudal raphe nuclei from 11 matched pairs of depressed suicide and control male subjects were processed for radioimmunocytochemistry using a primary antiserum to CRH and a I-[125]-IgG secondary antibody. The optical density corresponding to the level of CRH-immunoreactivity (IR) was quantified in specific pontine regions from the film autoradiographic images. The level of CRH-IR was increased by 30% in the locus coeruleus, 39% in the median raphe and 45% in the caudal dorsal raphe in the depressed suicide subjects compared to controls. No difference in CRH-IR was found in the dorsal tegmentum or medial parabrachial nucleus between the subject groups. These findings reveal that CRH-IR levels are specifically increased in norepinephrine- and serotonin-containing pontine nuclei of depressed suicide men, and thus they are consistent with the hypothesis that CRH neurotransmission is elevated in extra-hypothalamic brain regions of depressed subjects.