Messier Michelle L, Li Aihua, Nattie Eugene E
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
J Appl Physiol (1985). 2004 May;96(5):1909-19. doi: 10.1152/japplphysiol.00805.2003. Epub 2004 Jan 29.
Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO2 in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome (48). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO2 response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO2 before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO2 response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation (P < 0.001) between the percent change in the CO2 response and piglet age. Younger piglets showed an exaggerated CO2 response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO2 response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age (P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less (P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO2 response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2 sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.
延髓中缝5-羟色胺能神经元在培养中具有化学敏感性，且位于脑干血管附近。选择性损伤中缝5-羟色胺能神经元会降低成年大鼠清醒和睡眠时对全身性二氧化碳的通气反应。包括中缝在内的延髓5-羟色胺能系统异常与婴儿猝死综合征有关（48）。在本研究中，我们探究3至16日龄未麻醉新生仔猪延髓中缝和中缝外区域的5-羟色胺能神经元是否参与二氧化碳反应。通过全身体积描记法检测5-羟色胺能神经元被5-HT1A受体激动剂8-羟基-2-二正丙基氨基四氢萘（8-OH-DPAT）局部抑制之前和期间对5%二氧化碳的通气反应。如线性回归分析所示，8-OH-DPAT（人工脑脊液中10或30 mM）以年龄依赖性方式降低清醒时的二氧化碳反应，该分析显示二氧化碳反应变化百分比与仔猪年龄之间存在显著负相关（P < 0.001）。较年幼的仔猪表现出夸大的二氧化碳反应。用人工脑脊液进行对照透析对二氧化碳反应无显著影响。此外，8-OH-DPAT升高血压并降低心率，且与年龄无关（P < 0.05）。最后，8-OH-DPAT扰乱睡眠周期，使仔猪清醒时间增多、睡眠时间减少（P < 0.05）。由于睡眠数据不完整，无法检测睡眠时的二氧化碳反应。抑制延髓中缝和中缝外5-羟色胺能神经元会降低通气对二氧化碳的敏感性，并改变心血管变量和睡眠周期，这可能与婴儿猝死综合征有关。
