Activity-dependent Notch signaling in the hypothalamo-neurohypophysial system of adult mouse brains
Activity-dependent Notch signaling in the hypothalamo-neurohypophysial system of adult mouse brains
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成年小鼠大脑下丘脑-神经垂体系统中活动依赖性Notch信号传导
DOI：
10.1111/jne.12172
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发表时间：
2014
影响因子：
3.2
通讯作者：
S
中科院分区：
文献类型：
--
作者：
Mannari;T;Miyata;S
Notch信号在发育中的大脑细胞命运规范中起关键作用；然而，最近的研究表明，Notch信号也参与成人大脑突触可塑性的调节。在本研究中，我们检测了Notch3和δ样配体4 （DLL4）在成年小鼠下丘脑-神经垂体系统（HNS）中的表达。DLL4在视上核（SON）和室旁核（PVN）的表达高于邻近下丘脑区域。利用囊泡GABA转运体和谷氨酸转运体进行免疫组化双标记，发现DLL4定位于针对含精氨酸抗利尿素（AVP）和催产素（OXT）的大细胞神经元的生长树突的兴奋性和抑制性轴突扣亚群。在神经垂体（NH）中，DLL4在OXT -含AVP -轴突末梢表达，而不在AVP -含轴突末梢表达。Notch3在SON和PVN中含有AVP和OXT的大细胞神经元的体树突以及NH中的垂体细胞中表达。盐负荷的慢性生理刺激可显著提高AVP和OXT的释放，减少SON和PVN中DLL4免疫反应性轴突钮扣的数量。此外，慢性和急性渗透刺激促进Notch3的蛋白水解裂解，在HNS中产生Notch3的细胞内片段。因此，本研究证明了HNS中DLL4表达的活性依赖性降低和Notch3的蛋白水解裂解，表明Notch信号可能参与下丘脑核的突触相互作用和NH的神经胶质相互作用。
Notch signalling has a key role in cell fate specification in developing brains; however, recent studies have shown that Notch signalling also participates in the regulation of synaptic plasticity in adult brains. In the present study, we examined the expression of Notch3 and Delta‐like ligand 4 (DLL4) in the hypothalamic‐neurohypophysial system (HNS) of the adult mouse. The expression of DLL4 was higher in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) compared to adjacent hypothalamic regions. Double‐labelling immunohistochemistry using vesicular GABA transporter and glutamate transporter revealed that DLL4 was localised at a subpopulation of excitatory and inhibitory axonal boutons against somatodendrites of arginine vasopressin (AVP)‐ and oxytocin (OXT)‐containing magnocellular neurones. In the neurohypophysis (NH), the expression of DLL4 was seen at OXT‐ but not AVP‐containing axonal terminals. The expression of Notch3 was seen at somatodendrites of AVP‐ and OXT‐containing magnocellular neurones in the SON and PVN and at pituicytes in the NH. Chronic physiological stimulation by salt loading, which remarkably enhances the release of AVP and OXT, decreased the number of DLL4‐immunoreactive axonal boutons in the SON and PVN. Moreover, chronic and acute osmotic stimulation promoted proteolytic cleavage of Notch3 to yield the intracellular fragments of Notch3 in the HNS. Thus, the present study demonstrates activity‐dependent reduction of DLL4 expression and proteolytic cleavage of Notch3 in the HNS, suggesting that Notch signalling possibly participates in synaptic interaction in the hypothalamic nuclei and neuroglial interaction in the NH.