NMDA受体
海马结构
谷氨酸的
兴奋毒性
谷氨酸受体
神经保护
神经科学
生物
神经元
星形胶质细胞
受体
细胞生物学
化学
中枢神经系统
生物化学
作者
Jan Voldřich,Marika Matoušová,Markéta Šmídková,Barbora Slavı́ková,Hana Chodounská,Eva Kudová,Helena Mertlíková‐Kaiserová
标识
DOI:10.1016/j.ejphar.2022.175056
摘要
The goal of this study was to evaluate mixed cortical and hippocampal primary rat postnatal neuronal culture as in vitro tool for identification of N-methyl-D-aspartate receptor (NMDAR) antagonists and to find out, whether this model is comparable with other commonly used primary rat neuronal models differing in their origin (pure cortical vs. mixed cortical and hippocampal) and differentiation state (embryonal vs. postnatal). Induced pluripotent stem cell (iPSC) - derived human glutamatergic neurons have been included in this study as well. First, the cultures were characterized by their neuron/astrocyte composition, the mRNA expression of NR2B/NR2A NMDAR subunit ratios, and the expression of glutamate transporters (GLT1, GLAST). Then, selected endogenous steroids and synthetic neuroactive steroids that have been previously identified as negative allosteric modulators of recombinant GluN1/GluN2B NMDA receptors, were evaluated for their ability to prevent an NMDA or glutamate-induced Ca2+ influx (acute effect) and excitotoxicity over 24 h. Though the neuroprotective potential against excitotoxic stimuli varied among the models studied, postnatal mixed cortical and hippocampal culture proved to be a convenient and robust tool for NMDAR antagonist screening. The most widely used embryonal (E18) cultures offered higher cell yields but at the expense of a higher sensitivity to compounds' cytotoxicity. iPSC-derived neurons were not found to be superior to rat cultures for screening purposes.
科研通智能强力驱动
Strongly Powered by AbleSci AI