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首页> 外文期刊>The European Journal of Neuroscience >In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice
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In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice

机译：子宫内大麻素暴露会改变新生小鼠的呼吸和对低氧的反应

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摘要

Cannabis is one of the most commonly used recreational drugs at ages highly correlated with potential pregnancy. Endocannabinoid signalling regulates important stages of neuronal development. When cannabinoid receptors, which are widely distributed through the nervous system, are activated by exogenous cannabinoids, breathing in adult rats is depressed. Here, we show that, in newborn mice, endocannabinoids, through the activation of cannabinoid receptor type 1 (CB1R), participate in the modulation of respiration and its control. Blocking CB1Rs at birth suppressed the brake exerted by endocannabinoids on ventilation in basal and in hypoxic conditions. The number of apnoeas and their duration were also minimized by activation of CB1Rs in normoxic and in hypoxic conditions. However, prenatal cannabis intoxication, caused by a daily injection of WIN55,212-2, in pregnant mice durably modified respiration of the offspring, as shown by hyperventilation in basal conditions, an altered chemoreflex in response to hypoxia, and longer apnoeas. When CB1Rs were blocked in WIN55,212-2 treated newborns, persistent hyperventilation was still observed, which could partly be explained by a perturbation of the central respiratory network. In fact, in vitro medullary preparations from WIN55,212-2 treated pups, free of peripheral or of supramedullary structures, showed an altered fictive breathing frequency. In conclusion, the endocannabinoid pathway at birth seems to modulate breathing and protect the newborn against apnoeas. However, when exposed prenatally to an excess of cannabinoid, the breathing neuronal network in development seems to be modified, probably rendering the newborn more vulnerable in the face of an unstable environment. Cannabis is one of the most commonly used recreational drugs at ages highly correlated with potential pregnancies and long term effects on cognitive functions are clearly showed. We show that in utero exposure to cannabinoid modified both peripheral and central networks, which modulate the respiratory drive in newborn mice. Cannabinoid exposure during pregnancy renders the newborn more vulnerable in the face of an unstable environment.
机译：大麻是与潜在怀孕高度相关的年龄段中最常用的娱乐性药物之一。内源性大麻素信号传导调节神经元发育的重要阶段。当通过神经系统广泛分布的大麻素受体被外源性大麻素激活时，成年大鼠的呼吸就会受到抑制。在这里，我们显示，在新生小鼠中，内源性大麻素通过激活1型大麻素受体（CB1R）参与呼吸调节及其控制。在出生时阻断CB1Rs可抑制基础和低氧条件下内源性大麻素对通气产生的制动作用。通过在常氧和低氧条件下激活CB1R，还可将呼吸暂停的数量及其持续时间减至最少。但是，由于每天注射WIN55,212-2对怀孕小鼠造成的产前大麻中毒持久地改变了后代的呼吸，如在基础条件下过度换气，对缺氧的化学反射改变以及更长的呼吸暂停所表明的。当在接受WIN55,212-2治疗的新生儿中阻断CB1R时，仍然观察到持续的过度换气，这部分可以由中央呼吸网络的扰动来解释。实际上，由WIN55,212-2处理的幼犬的体外髓样制剂，没有外围或上髓腔结构，其假想呼吸频率发生了变化。总之，出生时的内源性大麻素途径似乎可以调节呼吸并保护新生儿免受呼吸暂停的影响。但是，当产前暴露于过量的大麻素时，发育中的呼吸神经网络似乎已被改变，可能使新生儿在不稳定的环境中更易受伤害。大麻是与潜在怀孕高度相关的年龄段中最常用的娱乐性药物之一，并且明确显示出对认知功能的长期影响。我们表明在子宫内接触大麻素会同时修饰外周和中央网络，从而调节新生小鼠的呼吸驱动。怀孕期间的大麻素暴露使新生儿面对不稳定的环境更加脆弱。

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