Black Emily A E, Smith Pauline M, McIsaac William, Ferguson Alastair V
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
Physiol Rep. 2018 May;6(10):e13704. doi: 10.14814/phy2.13704.
Brain-derived neurotrophic factor (BDNF), a neurotrophin traditionally associated with neural plasticity, has more recently been implicated in fluid balance and cardiovascular regulation. It is abundantly expressed in both the central nervous system (CNS) and peripheral tissue, and is also found in circulation. Studies suggest that circulating BDNF may influence the CNS through actions at the subfornical organ (SFO), a circumventricular organ (CVO) characterized by the lack of a normal blood-brain barrier (BBB). The SFO, well-known for its involvement in cardiovascular regulation, has been shown to express BDNF mRNA and mRNA for the TrkB receptor at which BDNF preferentially binds. This study was undertaken to determine if: (1) BDNF influences the excitability of SFO neurons in vitro; and (2) the cardiovascular consequences of direct administration of BDNF into the SFO of anesthetized rats. Electrophysiological studies revealed that bath application of BDNF (1 nmol/L) influenced the excitability of the majority of neurons (60%, n = 13/22), the majority of which exhibited a membrane depolarization (13.8 ± 2.5 mV, n = 9) with the remaining affected cells exhibiting hyperpolarizations (-11.1 ± 2.3 mV, n = 4). BDNF microinjections into the SFO of anesthetized rats caused a significant decrease in blood pressure (mean [area under the curve] AUC = -364.4 ± 89.0 mmHg × sec, n = 5) with no effects on heart rate (mean AUC = -12.2 ± 3.4, n = 5). Together these observations suggest the SFO to be a CNS site at which circulating BDNF could exert its effects on cardiovascular regulation.
脑源性神经营养因子（BDNF）是一种传统上与神经可塑性相关的神经营养因子，最近被认为与体液平衡和心血管调节有关。它在中枢神经系统（CNS）和外周组织中均有大量表达，在循环系统中也可检测到。研究表明，循环中的BDNF可能通过作用于穹窿下器（SFO）影响中枢神经系统，穹窿下器是一种室周器官（CVO），其特点是缺乏正常的血脑屏障（BBB）。SFO以参与心血管调节而闻名，已被证明可表达BDNF mRNA和TrkB受体mRNA，BDNF优先与该受体结合。本研究旨在确定：（1）BDNF在体外是否影响SFO神经元的兴奋性；（2）将BDNF直接注射到麻醉大鼠的SFO中对心血管系统的影响。电生理研究表明，浴槽中加入BDNF（1 nmol/L）可影响大多数神经元的兴奋性（60%，n = 13/22），其中大多数神经元表现为膜去极化（13.8±2.5 mV，n = 9），其余受影响细胞表现为超极化（-11.1±2.3 mV，n = 4）。向麻醉大鼠的SFO中微量注射BDNF可导致血压显著下降（平均[曲线下面积]AUC = -364.4±89.0 mmHg×秒，n = 5），而对心率无影响（平均AUC = -12.2±3.4，n = 5）。这些观察结果共同表明，SFO是循环中的BDNF可能对心血管调节发挥作用的中枢神经系统部位。
