Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii.
Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii.
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DOI：
10.1016/j.autneu.2012.11.008
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发表时间：
2013-04
影响因子：
2.7
通讯作者：
Lin, Li-Hsien
中科院分区：
文献类型：
--
作者：
Talman, William T.;Lin, Li-Hsien
为了评估P物质（SP）或儿茶酚胺传递被消除的大鼠的压力感受性反射和心血管反应，我们研究了双侧孤束核（NTS）注射SP或与皂草素缀合的稳定化SP（分别为SP-SAP或SSP-SAP）或与多巴胺-β-羟化酶抗体缀合的SAP（抗DBH-SAP）后的动物。我们发现，SP-和SSP-SAP消除NTS神经元表达SP神经激肽-1受体（NK 1 R），而抗DBH-SAP消除NTS神经元表达酪氨酸羟化酶（TH）和DBH。毒素是有选择性的。因此，SP-或SSP-SAP不消除NTS中的TH/DBH神经元，并且anti-DBH-SAP不消除NTS中的NK 1 R神经元。然而，每种毒素都会导致动脉血压的慢性不稳定性、压力反射功能减弱、心室易激惹、心肌细胞凝固性坏死，在某些动物中，还会导致与心搏停止相关的猝死。然而，当TH/DBH神经元被靶向并通过注射6-羟基多巴胺（6-OHDA）消除时，没有发生心血管或心脏变化。在此回顾的研究表明，选择性损害的NTS导致改变压力反射控制和心脏的变化，可能导致猝死。虽然研究结果可以支持SP或儿茶酚胺在压力反射传递中的作用，但NK 1 R与谷氨酸受体共定位的研究还没有得到证实。因此，当用SP-或SSP-SAP处理时，具有两者的神经元丢失。此外，用6-OHDA处理后，儿茶酚胺神经元的损失不影响心血管控制。因此，毒素的作用可能取决于SAP的作用，而与SAP缀合物对靶向神经元类型的作用无关。
In efforts to assess baroreflex and cardiovascular responses in rats in which substance P (SP) or catecholamine transmission had been eliminated we studied animals after bilateral injections into the nucleus tractus solitarii (NTS) of SP or stabilized SP (SSP) conjugated to saporin (SP-SAP or SSP-SAP respectively) or SAP conjugated to an antibody to dopamine-β-hydroxylase (anti-DBH-SAP). We found that SP- and SSP-SAP eliminated NTS neurons that expressed the SP neurokinin-1 receptor (NK1R) while anti-DBH-SAP eliminated NTS neurons expressing tyrosine hydroxylase (TH) and DBH. The toxins were selective. Thus SP-or SSP-SAP did not eliminate TH/DBH neurons and anti-DBH-SAP did not eliminate NK1R neurons in the NTS. Each toxin, however, led to chronic lability of arterial blood pressure, diminished baroreflex function, cardiac ventricular irritability, coagulation necrosis of cardiac myocytes and, in some animals, sudden death associated with asystole. However, when TH/DBH neurons were targeted and eliminated by injection of 6-hydroxydopamine (6-OHDA), none of the cardiovascular or cardiac changes occurred. The studies reviewed here reveal that selective lesions of the NTS lead to altered baroreflex control and to cardiac changes that may lead to sudden death. Though the findings could support a role for SP or catecholamines in baroreflex transmission neither is proven in that NK1R colocalizes with glutamate receptors. Thus neurons with both are lost when treated with SP- or SSP-SAP. In addition, loss of catecholamine neurons after treatment with 6-OHDA does not affect cardiovascular control. Thus, the effect of the toxins may depend on an action of SAP independent of the effects of the SAP conjugates on targeted neuronal types.
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