More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides
More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides
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DOI：
10.1016/j.brainres.2005.01.083
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发表时间：
2005-04-11
期刊：
影响因子：
2.9
通讯作者：
Arango, V
中科院分区：
文献类型：
--
作者：
Boldrini, M;Underwood, MD;Arango, V
自杀者的脑干5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）减少，5-HT 1A自身受体减少，皮质5-羟色胺转运体结合减少，表明自杀中5-羟色胺神经传递不足。色氨酸羟化酶（TPH）是5-HT合成的限速酶，TPH的改变可以解释这些发现。我们试图确定自杀者和对照组中缝背核（DRN）和中缝正中核（MRN）中TPH免疫反应（TPH-IR）的量。在尸检时收集自杀者和对照组（n = 11对）的脑干，按年龄、性别和死后时间匹配，冷冻并切片（20 μ m）。使用抗体标记TPH进行免疫放射自显影，将载玻片暴露于胶片，并通过基于计算机的图像分析系统定量放射自显影。我们在整个核的长度上每1000 μ m检查一次切片，只对中缝完整的受试者进行统计分析TPH-IR（μ Ci/g）自杀组高于对照组（S：300.8 +/-70.8 vs. C：259.6 +/- 40.7，t = 2.57，df = 7，P = 0.04），自杀组和对照组之间无差异（S：251.3 ± 44.2 vs. C：235.9 ± 27.4，t = 1.49，df = 7，P = 0.18）。与男性对照组相比，男性自杀受害者（MS）的DRN TPH-IR更高（MC; MS：318.4 +/- 54.4 vs. MC：271.9 +/-22.5，t = 2.66，df = 6，P = 0.03）。TPH-IR的面积和密度的分析表明，与对照组相比，自杀者的吻侧DRN的面积和密度较高，尾侧DRN的面积和密度较低。更多的TPH可能是对受损的5-羟色胺释放或更少的自身受体激活的上调稳态反应。或者，自杀中的5-羟色胺损伤可能是由于功能低下的降钙素合成酶。(c)2005年由Elsevier B. V.出版
Deficient serotonin neurotransmission in suicide is indicated by reduced brainstem serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), fewer 5-HT1A autoreceptors and reduced cortical serotonin transporter binding in suicide victims. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of 5-HT, and alterations in TPH could explain some of these findings. We sought to determine the amount of TPH immunoreactivity (TPH-IR) in the dorsal (DRN) and median (MRN) raphe nuclei in suicides and controls.Brainstems of suicide victims and controls (n = 11 pairs) were collected at autopsy, matched for age, sex and postmortem interval, frozen and sectioned (20 mu m). Immunoautoradiography, using an antibody to label TPH, was performed, slides exposed to film and autoradiograms quantified by a computer-based image analysis system. We examined sections every 1000 mu m throughout the whole length of the nucleus, performing statistical analysis only on those subjects for whom the raphe was complete (n = 8 pairs).TPH-IR (mu Ci/g) was higher in suicides than controls (S: 300.8 +/- 70,8 vs. C: 259.6 +/- 40.7, t = 2.57, df = 7, P = 0.04) in the dorsal raphe nucleus (DRN), and not different between suicides and controls (S: 251.3 +/- 44.2 vs. C: 235.9 +/- 27.4, t = 1.49, df = 7, P = 0.18) in the MRN. DRN TPH-IR was higher in male suicide victims (MS) compared to male controls (MC; MS: 318.4 +/- 54.4 vs. MC: 271.9 +/- 22,5, t = 2.66, df = 6, P = 0.03). The analysis of TPH-IR area and density at each DRN rostrocaudal levels showed higher area and density in suicides compared to controls in the rostral DRN and lower area and density in the caudal DRN.TPH-IR, an index of the amount of TPH enzyme, in the DRN is higher in depressed suicides. More TPH may be an upregulatory homeostatic response to impaired serotonin release or less autoreceptor activation. Alternatively, the serotonin impairment in suicide may be due to hypofunctional serotonin-synthesizing enzyme. (c) 2005 Published by Elsevier B.V.