Postnatal loss of brainstem serotonin neurones compromises the ability of neonatal rats to survive episodic severe hypoxia
Postnatal loss of brainstem serotonin neurones compromises the ability of neonatal rats to survive episodic severe hypoxia
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DOI：
10.1113/jphysiol.2011.214445
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发表时间：
2011-11-01
影响因子：
5.5
通讯作者：
Nattie, Eugene E.
中科院分区：
文献类型：
--
作者：
Cummings, Kevin J.;Hewitt, Julie C.;Nattie, Eugene E.
Pet-1（-/-）小鼠与产前，遗传诱导的5-羟色胺（5-HT，5-羟色胺）神经元的损失是在他们的能力，以承受间歇性环境缺氧通过自我复苏受损。鉴于5-HT神经元在神经网络发育中的产前作用，在这里，我们要问的是，出生后5-HT神经元的丢失是否也会影响自动复苏。我们用脑池内注射5，7-二羟色胺（5，7-DHT;类似于40 μ g; n = 8）或载体（对照; n = 14）治疗出生后第2-3天的新生大鼠幼仔，以防止5-HT系统的损伤。在P7-10，我们将未麻醉的治疗和对照幼仔暴露于15次环境缺氧（97% N-2，3% CO2）。5，7-二氢睾酮处理后，脊髓5-HT含量降低80%（P < 0.001）。与对照组相比，5-HT缺乏幼崽的基线通气量（（V）对点（E））、代谢率（（V）对点（O2））、呼吸当量（（V）对点（E）/（V）对点（O2））、心率（HR）、心率变异性（HRV）和动脉血红蛋白饱和度（S-aO 2）无差异。然而，只有25%的5-HT-缺乏的幼崽生存的所有15次环境缺氧，相比之下，79%的控制窝（P = 0.007）。5，7-DHT处理的幼仔的高死亡率与喘息发作延迟（P < 0.001）、缺氧诱导的心动过缓HR恢复延迟（P < 0.001）和缺氧诱导的呼吸暂停正常呼吸恢复延迟（P < 0.001）相关。5，7-DHT治疗既不影响开始时的喘息模式，也不影响室内空气干预期间的HR、（V）对点（E）/（V）对点（O2）或S-aO 2。HRV的显着增加发生在所有动物重复暴露，并在5-HT缺乏的幼崽，这种增加发生在死亡前。我们的结论是，出生后脑干5-HT含量的损失损害自动复苏反应环境缺氧。这份报告提供了新的证据，在大鼠幼鼠5-羟色胺神经元在自动复苏的生理作用。我们的数据可能与了解婴儿猝死综合征（SIDS）的病因有关，其中存在髓质5-HT缺乏，在某些情况下存在严重缺氧和自动复苏失败的证据。
Pet-1(-/-) mice with a prenatal, genetically induced loss of 5-hydroxytryptamine (5-HT, serotonin) neurones are compromised in their ability to withstand episodic environmental anoxia via autoresuscitation. Given the prenatal role of 5-HT neurones in the development of neural networks, here we ask if a postnatal loss of 5-HT neurones also compromises autoresuscitation. We treated neonatal rat pups at postnatal day (P) 2-3 with an intra-cisternal injection of 5,7-dihydroxytryptamine (5,7-DHT; similar to 40 mu g; n = 8) to pharmacologically lesion the 5-HT system, or vehicle (control; n = 14). At P7-10 we exposed unanaesthetized treated and control pups to 15 episodes of environmental anoxia (97% N-2, 3% CO2). Medullary 5-HT content was reduced 80% by 5,7-DHT treatment (P < 0.001). Baseline ventilation ((V)over dot(E)), metabolic rate ((V)over dot(O2)), ventilatory equivalent ((V)over dot(E)/(V)over dot(O2)), heart rate (HR), heart rate variability (HRV) and arterial haemoglobin saturation (S-aO2) were no different in 5-HT-deficient pups compared to controls. However, only 25% of 5-HT-deficient pups survived all 15 episodes of environmental anoxia, compared to 79% of control littermates (P = 0.007). High mortality of 5,7-DHT-treated pups was associated with delayed onset of gasping (P < 0.001), delayed recovery of HR from hypoxic-induced bradycardia (P < 0.001), and delayed recovery of eupnoea from hypoxic-induced apnoea (P < 0.001). Treatment with 5,7-DHT affected neither the gasping pattern once initiated, nor HR, (V)over dot(E)/(V)over dot(O2) or S-aO2 during the intervening episodes of room air. A significant increase in HRV occurred in all animals with repeated exposure, and in 5-HT-deficient pups this increase occurred immediately prior to death. We conclude that a postnatal loss of brainstem 5-HT content compromises autoresuscitation in response to environmental anoxia. This report provides new evidence in rat pups that 5-HT neurones serve a physiological role in autoresuscitation. Our data may be relevant to understanding the aetiology of the sudden infant death syndrome (SIDS), in which there is medullary 5-HT deficiency and in some cases evidence of severe hypoxia and failed autoresuscitation.