Identification of N-methyl-D-aspartate receptor antagonists using the rat postnatal mixed cortical and hippocampal neurons

0558330 - ÚOCHB 2023 RIV NL eng J - Článek v odborném periodiku
Voldřich, Jan - Matoušová, Marika - Šmídková, Markéta - Slavíková, Barbora - Chodounská, Hana - Kudová, Eva - Mertlíková-Kaiserová, Helena
Identification of N-methyl-D-aspartate receptor antagonists using the rat postnatal mixed cortical and hippocampal neurons.
European Journal of Pharmacology. Roč. 927, July (2022), č. článku 175056. ISSN 0014-2999. E-ISSN 1879-0712
Grant CEP: GA TA ČR(CZ) TN01000013
Institucionální podpora: RVO:61388963
Klíčová slova: NMDA receptors * primary neurons * iPSC * neurosteroids
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1016/j.ejphar.2022.175056

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.
Trvalý link: http://hdl.handle.net/11104/0332052