Hypoxia-induced Fos expression in neurons projecting to the pressor region in the rostral ventrolateral medulla
Hypoxia-induced Fos expression in neurons projecting to the pressor region in the rostral ventrolateral medulla
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DOI：
10.1016/s0306-4522(97)00111-5
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发表时间：
1997-10-01
期刊：
影响因子：
3.3
通讯作者：
Dampney, RAL
中科院分区：
文献类型：
--
作者：
Hirooka, Y;Polson, JW;Dampney, RAL
以往在麻醉动物中的研究表明，缺氧引起的交感神经血管活性的增加在很大程度上依赖于延髓腹外侧头端交感神经兴奋性加压神经元的突触兴奋。本研究的主要目的是确定，在清醒的兔子，脑内的神经元的分布，具有特性的interneurons传递兴奋性输入的头端腹外侧髓压区响应全身缺氧。在初步操作中;将逆行转运的示踪剂、荧光标记的微球注射到延髓头端腹外侧的生理学鉴定的加压区中。经过一至两周的等待期，清醒的兔子进行中度缺氧（诱导呼吸10%O-2的N-2）的一段时间为60分钟。对照组的动物暴露于室内空气或轻度缺氧（12%O-2的N-2）。中度缺氧导致约15 mmHg的中度高血压，Fos表达增加。（神经元激活的标志物）在孤束核、延髓腹外侧的吻侧、中间和尾侧部分、Kolliker-Eklobus核、蓝斑、蓝斑下和围栏中的A5区以及几个中脑和前脑区域中的许多神经元中，包括中脑的导水管周围灰质和下丘脑的室旁核、视上核和弓状核。在轻度缺氧或常氧条件下，Fos蛋白在上述脑区也有表达，但与中度缺氧条件下相比，Fos蛋白表达明显减少。在中度缺氧后，大约一半的延髓腹外侧区神经元，27%的孤束核神经元，以及49-81%的蓝斑、蓝斑下和A5区的神经元表达Fos，它们也对酪氨酸羟化酶呈免疫反应性，因此是儿茶酚胺细胞。大约有一半的神经元在孤束核和三分之二的神经元在Kolliker-Ehrmann核，表达Fos中度缺氧后逆行标记的头端腹外侧髓压区。同样，大约四分之一的Fos阳性细胞在尾侧和中间腹外侧髓质逆行标记，但很少Fos阳性/逆行标记的细胞被发现在其他脑桥延髓或suprapontine脑regions.The结果表明，系统性缺氧的结果在几个离散的核在脑干和前脑，包括在所有主要的脑桥延髓儿茶酚胺细胞群的神经元的激活。然而，被全身性缺氧激活并投射到头端腹外侧延髓加压区的神经元实际上仅限于下脑干，主要在孤束核和Kolliker-Bronchus核中，在较小程度上在尾侧/中间腹外侧延髓中。在我们实验室以前的一项研究中，我们确定了高血压激活的脑干神经元的分布，这些神经元也投射到头端腹外侧延髓加压区。[Poison et ni.等（1995）Neuroscience 67，107-123]。本研究结果与以往的研究结果比较表明，孤束核和Kolliker-Kellnucleus中向延髓头端腹外侧投射的低氧激活神经元可能是传递兴奋性化学感受器信号的中间神经元，而延髓尾侧/中间腹外侧投射的低氧激活神经元可能主要是传递抑制性压力感受器信号的中间神经元，由与缺氧诱导的高血压相关的动脉血压升高激活。(C)1997年IBRO。出版社：Elsevier Science Ltd
Previous studies in anaesthetized animals have shown that the hypoxia-induced increase in sympathetic vasomotor activity is largely dependent on synaptic excitation of sympathoexcitatory presser neurons in the rostral part of the ventrolateral medulla. The primary aim of this study was to determine, in conscious rabbits, the distribution of neurons within the brain that have properties characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary presser region in response to systemic hypoxia. In a preliminary operation; a retrogradely-transported tracer, fluorescent-labelled microspheres, was injected into the physiologically-identified presser region in the rostral ventrolateral medulla. After a waiting period of one to two weeks, the conscious rabbits were subjected to moderate hypoxia (induced by breathing 10% O-2 in N-2) for a period of 60 min. Control groups of animals were exposed to room air or to mild hypoxia (12% O-2 in N-2). Moderate hypoxia resulted in a modest hypertension of approximately 15 mmHg, and in the expression of Fos (a marker of neuronal activation) in many neurons in the nucleus tractus solitarius, the rostral, intermediate and caudal parts of the ventrolateral medulla, the Kolliker-Fuse nucleus, locus coeruleus, subcoeruleus and A5 area in the pens as well as in several midbrain and forebrain regions, including the periaqueductal grey in the midbrain and the paraventricular, supraoptic and arcuate nuclei in the hypothalamus. Fos expression was also observed in these regions in rabbits subjected to mild hypoxia or normoxia, but it was much reduced compared to rabbits subjected to moderate hypoxia. Approximately half of the neurons in the ventrolateral medulla, 27% of neurons in the nucleus tractus solitarius, and 49-81% of neurons in the locus coeruleus, sub-coeruleus and A5 area that expressed Fos following moderate hypoxia were also immunoreactive For tyrosine hydroxylase, and were therefore catecholamine cells. Approximately half of the neurons in the nucleus tractus solitarius and two-thirds of neurons in the Kolliker-Fuse nucleus that expressed Fos following moderate hypoxia were retrogradely labelled from the rostral ventrolateral medullary presser region. Similarly, approximately one quarter of Fos-positive cells in the caudal and intermediate ventrolateral medulla were retrogradely labelled, but very few Fos-positive/retrogradely-labelled cells were found in other pontomedullary or suprapontine brain regions.The results indicate that systemic hypoxia results in activation of neurons in several discrete nuclei in the brainstem and forebrain, including neurons in all the major pontomedullary catecholamine cell groups. However, neurons that are activated by systemic hypoxia and that also project to the rostral ventrolateral medullary pressor region are virtually confined to the lower brainstem, primarily in the nucleus tractus solitarius and Kolliker-Fuse nucleus and to a lesser extent the caudal/intermediate ventrolateral medulla. In a previous study from our laboratory, we determined the distribution of neurons in the brainstem that are activated by hypertension and that also project to the rostral ventrolateral medullary presser region. [Poison et ni. (1995) Neuroscience 67, 107-123]. Comparison of the present results with those from this previous study indicates that the hypoxia-activated neurons in the nucleus tractus solitarius and Kolliker-Fuse nucleus that project to the rostral ventrolateral medulla are likely to be interneurons conveying excitatory chemoreceptor signals, while those in the caudal/intermediate ventrolateral medulla are likely to be mainly interneurons conveying inhibitory baroreceptor signals, activated by the rise in arterial blood pressure associated with the hypoxia-induced hypertension. (C) 1997 IBRO. Published by Elsevier Science Ltd.