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

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00558330" target="_blank" >RIV/61388963:_____/22:00558330 - isvavai.cz</a>

  • Result on the web

    <a href="https://doi.org/10.1016/j.ejphar.2022.175056" target="_blank" >https://doi.org/10.1016/j.ejphar.2022.175056</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.ejphar.2022.175056" target="_blank" >10.1016/j.ejphar.2022.175056</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/TN01000013" target="_blank" >TN01000013: Personalized Medicine – Diagnostics and Therapy</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    European Journal of Pharmacology

  • ISSN

    0014-2999

  • e-ISSN

    1879-0712

  • Volume of the periodical

    927

  • Issue of the periodical within the volume

    July

  • Country of publishing house

    NL - THE KINGDOM OF THE NETHERLANDS

  • Number of pages

    12

  • Pages from-to

    175056

  • UT code for WoS article

    000809747800002

  • EID of the result in the Scopus database

    2-s2.0-85131435177