Bright Fiona M, Byard Roger W, Vink Robert, Paterson David S
Faculty of Health and Medical Science, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
J Neuropathol Exp Neurol. 2017 Oct 1;76(10):864-873. doi: 10.1093/jnen/nlx071.
Serotonin (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to key autonomic and respiratory nuclei in the brainstem and spinal cord regulating critical homeostatic functions. Multiple abnormalities in markers of 5-HT function in the medulla in sudden infant death syndrome (SIDS) have been reported, informing the hypothesis that at least a subset of SIDS cases is caused by deficits in 5-HT function resulting in impaired homeostatic responses to potentially life-threatening events during sleep. To investigate medullary 5-HT defects in SIDS further, we undertook qualitative analysis immunohistochemical assessment of 5-HT neuron expression within the medulla of SIDS infants (n41) and nonSIDS controls (n = 28) in an independent cohort from Forensic Science South Australia. Compared with controls SIDS cases had significantly higher 5-HT neuron numbers and density in addition to significantly altered 5-HT neuron morphology. Thus, for the first time, we replicated and corroborated previous observations of a significant abnormality in medullary 5-HT neuron expression in SIDS in a separate independent SIDS cohort. This study further supports the hypothesis that medullary 5-HT defects contribute to the pathogenesis of a subset of SIDS victims and provides additional evidence of a more complex abnormality in 5-HT neuron dysfunction specifically within the different caudal and rostral medullary 5-HT domains.
延髓中的5-羟色胺(5-羟色胺[5-HT])神经元广泛投射到脑干和脊髓中的关键自主神经和呼吸核,调节关键的稳态功能。已有报道称,婴儿猝死综合征(SIDS)患者延髓中5-HT功能标志物存在多种异常,这支持了一种假说,即至少一部分SIDS病例是由5-HT功能缺陷引起的,导致在睡眠期间对潜在危及生命事件的稳态反应受损。为了进一步研究SIDS中的延髓5-HT缺陷,我们对来自南澳大利亚法医科学的一个独立队列中的SIDS婴儿(n = 41)和非SIDS对照(n = 28)的延髓内5-HT神经元表达进行了定性分析免疫组化评估。与对照组相比,SIDS病例除了5-HT神经元形态有显著改变外,5-HT神经元数量和密度也显著更高。因此,我们首次在一个单独的独立SIDS队列中重复并证实了先前关于SIDS中延髓5-HT神经元表达存在显著异常的观察结果。这项研究进一步支持了延髓5-HT缺陷导致一部分SIDS受害者发病机制的假说,并提供了额外证据,证明5-HT神经元功能障碍存在更复杂的异常,特别是在延髓不同的尾侧和头侧5-HT区域内。