In the Telencephalon, GluN2C NMDA Receptor Subunit mRNA is Predominately Expressed in Glial Cells and GluN2D mRNA in Interneurons.

In the Telencephalon, GluN2C NMDA Receptor Subunit mRNA is Predominately Expressed in Glial Cells and GluN2D mRNA in Interneurons.
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DOI:
10.1007/s11064-018-2526-7
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发表时间:
2019-01
影响因子:
4.4
通讯作者:
Monaghan DT
Monaghan DT
中科院分区:
医学3区
文献类型:
--
作者:
Alsaad HA;DeKorver NW;Mao Z;Dravid SM;Arikkath J;Monaghan DT

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N-甲基-D-天冬氨酸受体(NMDAR)广泛分布于脑中,在端脑中具有高浓度,在端脑中它们调节突触可塑性、工作记忆和其他功能。虽然主要GluN 2 NMDAR亚基GluN 2A和GluN 2B的作用已相对较好地了解,但端脑中GluN 2C和GluN 2D亚基的功能在很大程度上尚不清楚。为了更好地了解GluN 2C亚基的可能作用,我们使用荧光原位杂交(FISH)结合多种细胞标记物来确定表达GluN 2C mRNA的细胞的分布和类型。使用GluN 2C-KO小鼠作为阴性对照,仅在海马、纹状体、杏仁核和大脑皮层的非神经元细胞(NeuN阴性细胞)中发现GluN 2C mRNA表达。对于这些区域,GFAP阳性细胞的显著部分也表达GluN 2C mRNA。总体而言,端脑,苍白球和嗅球是唯一的区域,GluN 2C在神经元中表达。与GluN 2C相反,GluN 2D亚基mRNA与端脑中的神经元而非星形胶质细胞标记物或GluN 2C mRNA共定位(苍白球除外)。然而,GluN 2C mRNA与GluN 2D共定位于丘脑中,在丘脑中发现神经元GluN 2C表达。这些发现强烈表明,GluN 2C在端脑中具有非常独特的功能,与其在其他脑区域中的作用相比,以及与其他含GluN 2的NMDAR相比。含有GluN 2C的NMDARs可能在调节星形胶质细胞释放L-谷氨酸或D-丝氨酸以响应突触活动的L-谷氨酸溢出中具有特定作用。
N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain with high concentrations in the telencephalon where they modulate synaptic plasticity, working memory, and other functions. While the actions of the predominate GluN2 NMDAR subunits, GluN2A and GluN2B are relatively well understood, the function of GluN2C and GluN2D subunits in the telencephalon is largely unknown. To better understand the possible role of GluN2C subunits, we used fluorescence in situ hybridization (FISH) together with multiple cell markers to define the distribution and type of cells expressing GluN2C mRNA. Using a GluN2C-KO mouse as a negative control, GluN2C mRNA expression was only found in non-neuronal cells (NeuN-negative cells) in the hippocampus, striatum, amygdala, and cerebral cortex. For these regions, a significant fraction of GFAP-positive cells also expressed GluN2C mRNA. Overall, for the telencephalon, the globus pallidus and olfactory bulb were the only regions where GluN2C was expressed in neurons. In contrast to GluN2C, GluN2D subunit mRNA colocalized with neuronal and not astrocyte markers or GluN2C mRNA in the telencephalon (except for the globus pallidus). GluN2C mRNA did, however, colocalize with GluN2D in the thalamus where neuronal GluN2C expression is found. These findings strongly suggest that GluN2C has a very distinct function in the telencephalon compared to its role in other brain regions and compared to other GluN2-containing NMDARs. NMDARs containing GluN2C may have a specific role in regulating L-glutamate or D-serine release from astrocytes in response to L-glutamate spillover from synaptic activity.
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