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Prenatal intermittent hypoxia sensitizes the laryngeal chemoreflex, blocks serotoninergic shortening of the reflex, and reduces 5-HT3 receptor binding in the NTS in anesthetized rat pups.
Experimental Neurology ( IF 4.6 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.expneurol.2019.113166
William T Donnelly 1 , Robin L Haynes 2 , Kathryn G Commons 3 , Drexel J Erickson 2 , Chris M Panzini 3 , Luxi Xia 1 , Q Joyce Han 1 , J C Leiter 1
Affiliation  

We tested the hypothesis that exposure to intermittent hypoxia (IH) during pregnancy would prolong the laryngeal chemoreflex (LCR) and diminish the capacity of serotonin (5-hydroxytryptamine; 5-HT) to terminate the LCR. Prenatal exposure to IH was associated with significant prolongation of the LCR in younger, anesthetized, postnatal day (P) rat pups age P8 to P16 compared to control, room air (RA)-exposed rat pups of the same age. Serotonin microinjected into the NTS shortened the LCR in rat pups exposed to RA during gestation, but 5-HT failed to shorten the LCR in rat pups exposed to prenatal IH. Given these observations, we tested the hypothesis that prenatal hypoxia would decrease binding to 5-HT3 receptors in the nucleus of the solitary tract (NTS) where 5-HT acts to shorten the LCR. Serotonin 3 receptor binding was reduced in younger rat pups exposed to IH compared to control, RA-exposed rat pups in the age range P8 to P12. Serotonin 3 receptor binding was similar in older animals (P18-P24) regardless of gas exposure during gestation. The failure of the 5-HT injected into the NTS to shorten the LCR was correlated with a developmental decrease in 5-HT3 receptor binding in the NTS associated with exposure to prenatal IH. In summary, prenatal IH sensitized reflex apnea and blunted processes that terminate reflex apneas in neonatal rat pups, processes that are essential to prevent death following apneas such as those seen in babies who died of SIDS.

中文翻译:

产前间歇性缺氧使喉部化学反射敏感,阻止血清素能反射缩短,并减少麻醉幼鼠 NTS 中 5-HT3 受体的结合。

我们测试了这样的假设:怀孕期间暴露于间歇性缺氧 (IH) 会延长喉化学反射 (LCR) 并降低血清素(5-羟色胺;5-HT)终止 LCR 的能力。与对照组、暴露于室内空气 (RA) 的同龄大鼠幼崽相比,产前暴露于 IH 与年龄 P8 至 P16 的年轻、麻醉、出生后日 (P) 大鼠幼崽的 LCR 显着延长相关。微量血清素注射到 NTS 中可以缩短妊娠期间暴露于 RA 的幼鼠的 LCR,但 5-HT 未能缩短暴露于产前 IH 的幼鼠的 LCR。鉴于这些观察结果,我们测试了以下假设:产前缺氧会减少与孤束核 (NTS) 中 5-HT3 受体的结合,其中 5-HT 会缩短 LCR。与对照、暴露于 RA 的 P8 至 P12 幼鼠相比,暴露于 IH 的年轻幼鼠的血清素 3 受体结合减少。无论妊娠期间气体暴露如何,老年动物 (P18-P24) 的血清素 3 受体结合相似。注射到 NTS 中的 5-HT 未能缩短 LCR,这与 NTS 中 5-HT3 受体结合的发育减少有关,而 NTS 中的 5-HT3 受体结合与暴露于产前 IH 相关。总之,产前 IH 使新生大鼠幼仔的反射性呼吸暂停变得敏感,并减弱了终止反射性呼吸暂停的过程,这些过程对于防止呼吸暂停后死亡至关重要,例如死于 SIDS 的婴儿中所见的情况。
更新日期:2019-12-27
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