Horn E M, Kramer J M, Waldrop T G
Department of Molecular and Integrative Physiology, Neuroscience Program, and College of Medicine, University of Illinois, Urbana, IL 61803, USA.
Neuroscience. 2000;99(4):711-20. doi: 10.1016/s0306-4522(00)00221-9.
The caudal hypothalamus is an important CNS site controlling cardiorespiratory integration during systemic hypoxia. Previous findings from this laboratory have identified caudal hypothalamic neurons of anesthetized rats that are stimulated during hypoxia. In addition, patch-clamp recordings in an in vitro brain slice preparation have revealed that there is an age-dependent response to hypoxia in caudal hypothalamic neurons. The present study utilized the expression of the transcription factor Fos as an indicator of neuronal depolarization to determine the hypoxic response of caudal hypothalamic neurons throughout postnatal development in conscious rats. Sprague-Dawley rats, aged three to 56 days, were placed in a normobaric chamber circulated with either 10% oxygen or room air for 3h. Following the hypoxic/normoxic exposure period, tissues from the caudal hypothalamus, periaqueductal gray, rostral ventrolateral medulla and nucleus tractus solitarius were processed immunocytochemically for the presence of the Fos protein. There was a significant increase in the density of neurons expressing Fos in the caudal hypothalamus of hypoxic compared to normoxic adult rats that was maintained in the absence of peripheral chemoreceptors. In contrast, no increase in the density of Fos-expressing caudal hypothalamic neurons was observed during hypoxia in rats less than 12 days old. Increases in Fos expression were also observed in an age-dependent manner in the periaqueductal gray, rostral ventrolateral medulla and nucleus tractus solitarius. These results show an increase in Fos expression in caudal hypothalamic neurons during hypoxia in conscious rats throughout development, supporting the earlier in vitro reports suggesting that these neurons are stimulated by hypoxia.
尾侧下丘脑是在全身性缺氧期间控制心肺整合的重要中枢神经系统部位。该实验室之前的研究结果已确定了麻醉大鼠尾侧下丘脑中在缺氧时受到刺激的神经元。此外，在体外脑片制备中的膜片钳记录显示，尾侧下丘脑神经元对缺氧存在年龄依赖性反应。本研究利用转录因子Fos的表达作为神经元去极化的指标，以确定清醒大鼠出生后发育过程中尾侧下丘脑神经元的缺氧反应。将3至56日龄的Sprague-Dawley大鼠置于分别用10%氧气或室内空气循环的常压舱中3小时。在缺氧/常氧暴露期后，对来自尾侧下丘脑、导水管周围灰质、延髓头端腹外侧和孤束核的组织进行免疫细胞化学处理，以检测Fos蛋白的存在。与常氧成年大鼠相比，缺氧成年大鼠尾侧下丘脑中表达Fos的神经元密度显著增加，且在没有外周化学感受器的情况下仍保持增加。相比之下，在小于12日龄的大鼠缺氧期间，未观察到尾侧下丘脑表达Fos的神经元密度增加。在导水管周围灰质、延髓头端腹外侧和孤束核中也观察到Fos表达以年龄依赖性方式增加。这些结果表明，在清醒大鼠整个发育过程中的缺氧期间，尾侧下丘脑神经元中的Fos表达增加，支持了早期体外研究报告，表明这些神经元受到缺氧刺激。
