Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.
MRC Centre for Synaptic Plasticity; School of Physiology, Pharmacology, Neurosciences; University of Bristol, Bristol, UK.
Sci Rep. 2017 Feb 17;7:42463. doi: 10.1038/srep42463.
A few hundred hypothalamic neurons form a complex network that controls reproduction in mammals by secreting gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH secretion are essential for pubertal onset. During the juvenile period, GnRH neurons undergo morphological remodeling, concomitantly achieving an increased responsiveness to kisspeptin, the main secretagogue of GnRH. However, the link between GnRH neuron activity and their morphology remains unknown. Here, we show that brain expression levels of Dmxl2, which encodes the vesicular protein rabconnectin-3α, determine the capacity of GnRH neurons to be activated by kisspeptin and estradiol. We also demonstrate that Dmxl2 expression levels control the pruning of GnRH dendrites, highlighting an unexpected role for a vesicular protein in the maturation of GnRH neuronal network. This effect is mediated by rabconnectin-3α in neurons or glial cells afferent to GnRH neurons. The widespread expression of Dmxl2 in several brain areas raises the intriguing hypothesis that rabconnectin-3α could be involved in the maturation of other neuronal populations.
数百个下丘脑神经元形成一个复杂的网络，通过分泌促性腺激素释放激素（GnRH）来控制哺乳动物的生殖。GnRH 分泌的及时的产后变化对于青春期的开始至关重要。在青少年时期，GnRH 神经元经历形态重塑，同时对 kisspeptin（GnRH 的主要分泌激素）的反应性增加。然而，GnRH 神经元活动与其形态之间的联系仍然未知。在这里，我们表明，编码囊泡蛋白 rabconnectin-3α 的 Dmxl2 的脑表达水平决定了 GnRH 神经元被 kisspeptin 和雌二醇激活的能力。我们还证明，Dmxl2 的表达水平控制着 GnRH 树突的修剪，突出了囊泡蛋白在 GnRH 神经元网络成熟中的意外作用。这种影响是由 GnRH 神经元传入的神经元或神经胶质细胞中的 rabconnectin-3α 介导的。Dmxl2 在几个脑区的广泛表达提出了一个有趣的假设，即 rabconnectin-3α 可能参与其他神经元群体的成熟。
