Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition
Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition
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DOI：
10.1126/science.1157871
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发表时间：
2008-07-04
期刊：
影响因子：
56.9
通讯作者：
Gross, Cornelius
中科院分区：
文献类型：
--
作者：
Audero, Enrica;Coppi, Elisabetta;Gross, Cornelius
婴儿猝死综合症是发达国家新生儿后期死亡的主要原因。尸检研究显示这些婴儿脑干中的血清素神经元发生了变化。然而，血清素稳态改变可能导致猝死的机制尚不清楚。我们研究了转基因小鼠中血清素 1A 自身受体可逆过度表达改变血清素神经元自身抑制能力的后果。过度表达的小鼠表现出偶发性心动过缓和体温过低，这些症状发生在有限的发育时期，并且经常进展至死亡。此外，过度表达的小鼠未能激活自主靶器官来应对环境挑战。这些发现表明，过度的血清素自身抑制是灾难性自主神经失调的危险因素，并提供了血清素稳态改变在婴儿猝死综合症中的作用机制。
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.