Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USA.
Cells. 2023 May 16;12(10):1399. doi: 10.3390/cells12101399.
Studies in zebrafish and rats show that embryonic ethanol exposure at low-moderate concentrations stimulates hypothalamic neurons expressing hypocretin/orexin (Hcrt) that promote alcohol consumption, effects possibly involving the chemokine Cxcl12 and its receptor Cxcr4. Our recent studies in zebrafish of Hcrt neurons in the anterior hypothalamus (AH) demonstrate that ethanol exposure has anatomically specific effects on Hcrt subpopulations, increasing their number in the anterior AH (aAH) but not posterior AH (pAH), and causes the most anterior aAH neurons to become ectopically expressed further anterior in the preoptic area (POA). Using tools of genetic overexpression and knockdown, our goal here was to determine whether Cxcl12a has an important function in mediating the specific effects of ethanol on these Hcrt subpopulations and their projections. The results demonstrate that the overexpression of Cxcl12a has stimulatory effects similar to ethanol on the number of aAH and ectopic POA Hcrt neurons and the long anterior projections from ectopic POA neurons and posterior projections from pAH neurons. They also demonstrate that knockdown of Cxcl12a blocks these effects of ethanol on the Hcrt subpopulations and projections, providing evidence supporting a direct role of this specific chemokine in mediating ethanol's stimulatory effects on embryonic development of the Hcrt system.
在斑马鱼和大鼠中的研究表明，低浓度到中等浓度的胚胎乙醇暴露会刺激表达食欲素/下丘脑泌素 (Hcrt) 的下丘脑神经元，从而促进酒精消费，其作用可能涉及趋化因子 Cxcl12 和其受体 Cxcr4。我们最近在斑马鱼中对下丘脑前区 (AH) 的 Hcrt 神经元的研究表明，乙醇暴露对 Hcrt 亚群具有特定的解剖学影响，在前区 AH (aAH) 增加了它们的数量，但在后区 AH (pAH) 没有增加，并且导致最前的 aAH 神经元在视前区 (POA) 中异常地向前表达。我们使用基因过表达和敲低的工具，目的是确定 Cxcl12a 是否在调节这些 Hcrt 亚群及其投射对乙醇的特定作用中具有重要功能。结果表明，Cxcl12a 的过表达对 aAH 和异位 POA Hcrt 神经元的数量以及异位 POA 神经元的长前向投射和 pAH 神经元的后向投射具有类似于乙醇的刺激作用。它们还表明，Cxcl12a 的敲低阻断了乙醇对 Hcrt 亚群和投射的这些作用，为该特定趋化因子在介导乙醇对 Hcrt 系统胚胎发育的刺激作用中提供了直接作用的证据。
