Role of NMDA Receptors in Adult Neurogenesis and Normal Development of the Dentate Gyrus
Role of NMDA Receptors in Adult Neurogenesis and Normal Development of the Dentate Gyrus
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DOI：
10.1523/eneuro.0566-20.2021
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发表时间：
2021-07-01
期刊：
影响因子：
3.4
通讯作者：
Tashiro, Ayumu
中科院分区：
文献类型：
--
作者：
Amellem, Ingrid;Yovianto, Glen;Tashiro, Ayumu
NMDA受体是谷氨酸受体的一种类型，其参与哺乳动物脑中神经元的功能、可塑性和发育。然而，NMDA受体如何促进成年神经发生和齿状回的发育尚不清楚。在这项研究中，我们调查这个问题，通过检查一个区域特异性敲除小鼠线，缺乏NR 1基因，编码NMDA受体的必需亚基，在颗粒细胞的齿状回（DG-NR 1 KO小鼠）。我们发现，在成年DG-NR 1 KO小鼠的背侧齿状回中，新生成的颗粒细胞的存活、细胞增殖和颗粒细胞层的大小显著减少。我们的研究结果还表明，从出生后三周开始，未成熟神经元的数量和颗粒细胞层的体积显着减少。DG-NR 1 KO小鼠在新奇抑制喂养和旷场试验期间也表现出立即早期基因Arc表达和行为受损。这些结果表明，颗粒细胞中的NMDA受体在成年脑中的成年神经发生中起作用，并有助于齿状回的正常发育。
The NMDA receptors are a type of glutamate receptors, which is involved in neuronal function, plasticity and development in the mammalian brain. However, how the NMDA receptors contribute to adult neurogenesis and development of the dentate gyrus is unclear. In this study, we investigate this question by examining a region-specific knock-out mouse line that lacks the NR1 gene, which encodes the essential subunit of the NMDA receptors, in granule cells of the dentate gyrus (DG-NR1KO mice). We found that the survival of newly-generated granule cells, cell proliferation and the size of the granule cell layer are significantly reduced in the dorsal dentate gyrus of adult DG-NR1KO mice. Our results also show a significant reduction in the number of immature neurons and in the volume of the granule cell layer, starting from three weeks of postnatal age. DG-NR1KO mice also showed impairment in the expression of an immediate early gene, Arc, and behavior during the novelty-suppressed feeding and open field test. These results suggest that the NMDA receptors in granule cells have a role in adult neurogenesis in the adult brain and contributes to the normal development of the dentate gyrus.