据7月4日的《科学》(Science)杂志报道说,调控激素5-羟色胺的一种脑受体的过分活跃会引起发育中小鼠的偶发性死亡,其特征令人想起人类的婴儿猝死综合症(SIDS)。SIDS是美国一岁以下婴儿死亡的最主要原因。人们长期以来一直怀疑5-羟色胺缺乏是一种风险因子,但是直到现在,人们还从来没有发现造成这种缺乏的原因是什么,尽管人们注意到某种被称作Htrla 的5-羟色胺调控因子在某些SIDS病例中有所下降。
Enrica Audero及其同事在小鼠中过度生产这种特别的Htrla调控因子。他们发现,5-羟色胺受体具有这种改变的的大多数小鼠会死于SIDS样综合症,其死亡时间发生在小鼠发育的一个有限的时间窗阶段中。这些发现表明,5-羟色胺调控的缺乏足以引起小鼠的死亡。他们提出,小鼠可以作为帮助诊断和预防SIDS的一种动物模型。
原始出处:
Science,Vol. 321. no. 5885, pp. 130 - 133,Enrica Audero,Cornelius Gross
Sporadic Autonomic Dysregulation and Death Associated with Excessive Serotonin Autoinhibition
Sudden infant death syndrome is the leading cause of death in the postneonatal period in developed countries. Postmortem studies show alterations in serotonin neurons in the brainstem of such infants. However, the mechanism by which altered serotonin homeostasis might cause sudden death is unknown. We investigated the consequences of altering the autoinhibitory capacity of serotonin neurons with the reversible overexpression of serotonin 1A autoreceptors in transgenic mice. Overexpressing mice exhibited sporadic bradycardia and hypothermia that occurred during a limited developmental period and frequently progressed to death. Moreover, overexpressing mice failed to activate autonomic target organs in response to environmental challenges. These findings show that excessive serotonin autoinhibition is a risk factor for catastrophic autonomic dysregulation and provide a mechanism for a role of altered serotonin homeostasis in sudden infant death syndrome.
1 Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.
2 Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale Giacoro Pieraccini 6, 50139 Firenze, Italy.
3 Laboratory of Behavioural Neuropharmacology, Sigma-Tau SpA, Via Pontina Kilometer 30.400, 00040 Pomezia, Italy.
* To whom correspondence should be addressed. E-mail: gross@embl.it


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