Ferguson Alastair V, Latchford Kevin J, Samson Willis K
Queen's University, Department of Physiology, Kingston, Ontario, K7L 3N6, Canada.
Expert Opin Ther Targets. 2008 Jun;12(6):717-27. doi: 10.1517/14728222.12.6.717.
The paraventricular nucleus of the hypothalamus (PVN) has emerged as one of the most important autonomic control centers in the brain, with neurons playing essential roles in controlling stress, metabolism, growth, reproduction, immune and other more traditional autonomic functions (gastrointestinal, renal and cardiovascular).
Traditionally the PVN was viewed as a nucleus in which afferent inputs from other regions were faithfully translated into changes in single specific outputs, whether neuroendocrine or autonomic. Here we present data which suggest that the PVN plays significant and essential roles in integrating multiple sources of afferent input and sculpting an integrated autonomic output by concurrently modifying the excitability of multiple output pathways. In addition, we highlight recent work that suggests that dysfunction of such intranuclear integrative circuitry contributes to the pathology of conditions such as hypertension and congestive heart failure.
This review highlights data showing that individual afferent inputs (subfornical organ), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways. We also highlight recent studies showing that modifications in this integrated circuitry may play significant roles in the pathology of diseases such as congestive heart failure and hypertension.
下丘脑室旁核(PVN)已成为大脑中最重要的自主神经控制中心之一,其中的神经元在控制应激、代谢、生长、繁殖、免疫以及其他更传统的自主神经功能(胃肠、肾脏和心血管功能)方面发挥着重要作用。
传统上,PVN被视为一个核团,来自其他区域的传入输入会被忠实地转化为单一特定输出(无论是神经内分泌输出还是自主神经输出)的变化。在此,我们展示的数据表明,PVN在整合多种传入输入源并通过同时改变多个输出通路的兴奋性来塑造整合的自主神经输出方面发挥着重要且关键的作用。此外,我们强调了最近的研究工作,这些研究表明这种核内整合回路的功能障碍会导致诸如高血压和充血性心力衰竭等病症的病理变化。
本综述强调的数据表明,个体传入输入(穹窿下器)、信号分子(食欲素、脂联素)和中间神经元(谷氨酸/γ-氨基丁酸)都有可能影响(并因此协调)多个PVN输出通路。我们还强调了最近的研究,这些研究表明这种整合回路的改变可能在诸如充血性心力衰竭和高血压等疾病的病理过程中发挥重要作用。