Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups.
Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups.
复制标题
DOI：
10.1523/eneuro.0393-17.2017
复制
发表时间：
2017-11
期刊：
影响因子：
3.4
通讯作者：
Kinkead R
中科院分区：
文献类型：
--
作者：
Baldy C;Chamberland S;Fournier S;Kinkead R
未成熟哺乳动物喉部附近液体的存在会触发长时间的呼吸暂停，伴有显著的O2去饱和和心动过缓。当过度时，这种反射（喉化学反射; LCR）可能是致命的。我们对异常LCR的起源了解有限，然而，围产期应激和男性是婴儿心肺衰竭的危险因素。由于在生命早期暴露于压力对大脑发育具有有害的和性别特异性的后果，因此呼吸反射容易受到神经内分泌功能障碍的影响是合理的。为了解决这个问题，我们测试了假设，即新生儿母亲分离（NMS）足以加剧麻醉大鼠幼崽中LCR诱导的心脏呼吸抑制。从出生后第3天至第12天，将应激幼仔与其母亲分开3 h/d。在P14-P15，对幼仔进行仪器监测呼吸、氧饱和度（Spo 2）和心率。通过在喉部附近注射水（10 µl）激活LCR。应激幼崽中LCR诱导的呼吸暂停时间比对照组更长; O2饱和度下降和心动过缓更为严重，尤其是在雄性中。NMS增加了自发性EPSC（sEPSC）的频率和振幅在男性的迷走神经背侧运动核（DMNV），但不是女性。在应激幼仔（仅雄性）中观察到的皮质酮和睾酮之间的正相关关系表明，应激对神经内分泌功能的破坏是异常LCR中基于性别的差异的关键。由于睾丸激素应用到髓质片增强EPSC振幅只在男性，我们建议，睾丸激素介导的增强DMNV内的突触连接有助于男性偏见的心脏呼吸抑制LCR激活后，在强调小狗。
The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O2 desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants. Because exposure to stress during early life has deleterious and sex-specific consequences on brain development it is plausible that respiratory reflexes are vulnerable to neuroendocrine dysfunction. To address this issue, we tested the hypothesis that neonatal maternal separation (NMS) is sufficient to exacerbate LCR-induced cardio-respiratory inhibition in anesthetized rat pups. Stressed pups were separated from their mother 3 h/d from postnatal days 3 to 12. At P14–P15, pups were instrumented to monitor breathing, O2 saturation (Spo2), and heart rate. The LCR was activated by water injections near the larynx (10 µl). LCR-induced apneas were longer in stressed pups than controls; O2 desaturations and bradycardias were more profound, especially in males. NMS increased the frequency and amplitude of spontaneous EPSCs (sEPSCs) in the dorsal motor nucleus of the vagus (DMNV) of males but not females. The positive relationship between corticosterone and testosterone observed in stressed pups (males only) suggests that disruption of neuroendocrine function by stress is key to sex-based differences in abnormal LCR. Because testosterone application onto medullary slices augments EPSC amplitude only in males, we propose that testosterone-mediated enhancement of synaptic connectivity within the DMNV contributes to the male bias in cardio-respiratory inhibition following LCR activation in stressed pups.