University of Colorado, School of Medicine, Department of Physiology and Biophysics, RC-1 North Tower, P18-7127, Mail Stop 8307, Aurora, CO 80045, USA.
Brain Res. 2011 May 4;1388:89-99. doi: 10.1016/j.brainres.2011.03.015. Epub 2011 Mar 31.
The supraoptic nucleus (SON) of the hypothalamus contains magnocellular neurosecretory neurons (MNC) which synthesize and release the peptide hormones vasopressin and oxytocin. Glutamate is a prominent excitatory neurotransmitter in the SON and regulates MNC excitability. NMDA receptors (NMDAR), a type of ionotropic glutamate receptor, mediate synaptic plasticity of MNCs and are necessary for characteristic burst firing patterns which serve to maximize hormone release. NMDARs are di- or tri-heteromeric complexes of NR1 and NR2 subunits. Receptor properties depend on NR2 subunit composition and variable splicing of NR1. We investigated the expression profile of NR1 and NR2 subunits in the SON at the mRNA and protein levels plus protein expression of NR1 splice variants in control and salt-loaded adult rats. There was robust mRNA expression of all subunits, with NR2D levels being the highest. At the protein level, NR1, NR2B, and NR2D were robustly expressed, while NR2A was weakly expressed. NR2C protein was not detected with either of the two antibodies tested. All four NR1 splice variant cassettes (N1, C1, C2, C2') were detected in the SON, although NR1 N1 expression was too low for accurate analysis. Three days of salt-loading did not alter mRNA, protein, or splice variant expression of NMDAR subunits in the SON. Robust NR2D protein expression has not been previously shown in MNCs and is uncommon in the adult brain. Although the functional significance of this unusual expression profile is unknown, it may contribute to important physiological characteristics of SON neurons, such as burst firing and resistance to excitotoxicity.
下丘脑的视上核（SON）包含合成和释放肽激素血管加压素和催产素的大细胞神经分泌神经元（MNC）。谷氨酸是 SON 中的一种主要兴奋性神经递质，调节 MNC 的兴奋性。NMDA 受体（NMDAR）是一种离子型谷氨酸受体，介导 MNC 的突触可塑性，对于最大限度地释放激素的特征爆发式放电模式是必要的。NMDAR 是 NR1 和 NR2 亚基的二聚体或三聚体复合物。受体特性取决于 NR2 亚基组成和 NR1 的可变剪接。我们研究了 NR1 和 NR2 亚基在 mRNA 和蛋白质水平以及对照和盐负荷成年大鼠 SON 中 NR1 剪接变异体的蛋白质表达的表达谱。所有亚基的 mRNA 表达都很丰富，NR2D 水平最高。在蛋白质水平上，NR1、NR2B 和 NR2D 表达丰富，而 NR2A 表达较弱。用两种测试的抗体均未检测到 NR2C 蛋白。在 SON 中检测到所有四个 NR1 剪接变异体盒（N1、C1、C2、C2'），尽管 NR1 N1 的表达太低，无法进行准确分析。盐负荷 3 天不会改变 SON 中 NMDAR 亚基的 mRNA、蛋白质或剪接变异体表达。强烈的 NR2D 蛋白表达以前未在 MNC 中显示，在成年大脑中也不常见。虽然这种不寻常的表达模式的功能意义尚不清楚，但它可能有助于 SON 神经元的重要生理特征，例如爆发式放电和抗兴奋性毒性。
