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婴儿猝死综合征中多个血清素能脑干异常。

Multiple serotonergic brainstem abnormalities in sudden infant death syndrome.

作者信息

Paterson David S, Trachtenberg Felicia L, Thompson Eric G, Belliveau Richard A, Beggs Alan H, Darnall Ryan, Chadwick Amy E, Krous Henry F, Kinney Hannah C

机构信息

Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA.

出版信息

JAMA. 2006 Nov 1;296(17):2124-32. doi: 10.1001/jama.296.17.2124.

Abstract

CONTEXT

The serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei in the brainstem and spinal cord and help regulate homeostatic function. Previously, abnormalities in 5-HT receptor binding in the medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary 5-HT dysfunction may be responsible for a subset of SIDS cases.

OBJECTIVE

To investigate cellular defects associated with altered 5-HT receptor binding in the 5-HT pathways of the medulla in SIDS cases.

DESIGN, SETTING, AND PARTICIPANTS: Frozen medullae from infants dying from SIDS (cases) or from causes other than SIDS (controls) were obtained from the San Diego Medical Examiner's office between 1997 and 2005. Markers of 5-HT function were compared between SIDS cases and controls, adjusted for postconceptional age and postmortem interval. The number of samples available for each analysis ranged from 16 to 31 for SIDS cases and 6 to 10 for controls. An exploratory analysis of the correlation between markers and 6 recognized risk factors for SIDS was performed.

MAIN OUTCOME MEASURES

5-HT neuron count and density, 5-HT(1A) receptor binding density, and 5-HT transporter (5-HTT) binding density in the medullary 5-HT system; correlation between these markers and 6 recognized risk factors for SIDS.

RESULTS

Compared with controls, SIDS cases had a significantly higher 5-HT neuron count (mean [SD], 148.04 [51.96] vs 72.56 [52.36] cells, respectively; P<.001) and 5-HT neuron density (P<.001), as well as a significantly lower density of 5-HT(1A) receptor binding sites (P<or=.01 for all 9 nuclei) in regions of the medulla involved in homeostatic function. The ratio of 5-HTT binding density to 5-HT neuron count in the medulla was significantly lower in SIDS cases compared with controls (mean [SD], 0.70 [0.33] vs 1.93 [1.25] fmol/mg, respectively; P = .001). Male SIDS cases had significantly lower 5-HT(1A) binding density in the raphé obscurus compared with female cases (mean [SD], 16.2 [2.0] vs 29.6 [16.5] fmol/mg, respectively; P = .04) or with male and female controls combined (mean [SD], 53.9 [19.8] fmol/mg; P = .005). No association was found between 5-HT neuron count or density, 5-HT(1A) receptor binding density, or 5-HTT receptor binding density and other risk factors.

CONCLUSIONS

Medullary 5-HT pathology in SIDS is more extensive than previously delineated, potentially including abnormal 5-HT neuron firing, synthesis, release, and clearance. This study also provides preliminary neurochemical evidence that may help explain the increased vulnerability of boys to SIDS.

摘要

背景

延髓中的血清素能(5-羟色胺[5-HT])神经元广泛投射至脑干和脊髓中的自主神经核和呼吸核,并有助于调节体内平衡功能。此前,已鉴定出死于婴儿猝死综合征(SIDS)的婴儿延髓中5-HT受体结合异常,提示延髓5-HT功能障碍可能是一部分SIDS病例的病因。

目的

研究SIDS病例延髓5-HT通路中与5-HT受体结合改变相关的细胞缺陷。

设计、地点和参与者:1997年至2005年间从圣地亚哥法医办公室获取死于SIDS的婴儿(病例)或死于SIDS以外原因的婴儿(对照)的冷冻延髓。比较SIDS病例和对照之间5-HT功能的标志物,并根据孕龄和死后间隔进行调整。SIDS病例每项分析可用样本数为16至31个,对照为6至10个。对标志物与6种公认的SIDS危险因素之间的相关性进行了探索性分析。

主要观察指标

延髓5-HT系统中的5-HT神经元计数和密度、5-HT(1A)受体结合密度以及5-HT转运体(5-HTT)结合密度;这些标志物与6种公认的SIDS危险因素之间的相关性。

结果

与对照相比,SIDS病例的5-HT神经元计数(均值[标准差]分别为148.04[51.96]个细胞和72.56[52.36]个细胞;P<.001)和5-HT神经元密度(P<.001)显著更高,而参与体内平衡功能的延髓区域中5-HT(1A)受体结合位点的密度显著更低(所有9个核均P≤.01)。与对照相比,SIDS病例延髓中5-HTT结合密度与5-HT神经元计数的比值显著更低(均值[标准差]分别为0.70[0.33]fmol/mg和1.93[1.25]fmol/mg;P =.001)。与女性病例相比(均值[标准差]分别为16.2[2.0]fmol/mg和29.6[16.5]fmol/mg;P =.04)或与男性和女性对照合并相比(均值[标准差]为53.9[19.8]fmol/mg;P =.005),男性SIDS病例中缝隐核的5-HT(1A)结合密度显著更低。未发现5-HT神经元计数或密度、5-HT(1A)受体结合密度或5-HTT受体结合密度与其他危险因素之间存在关联。

结论

SIDS中的延髓5-HT病理学比先前描述的更为广泛,可能包括5-HT神经元放电、合成、释放和清除异常。本研究还提供了初步的神经化学证据,可能有助于解释男孩患SIDS的易感性增加。

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