Evaluation of SK-N-SH Cells as a Model for NMDA Receptor Induced Toxicity.
Gunnar Goerges, Paul Disse, Stefan Peischard, Nadine Ritter, Christoph Brenker, Guiscard Seebohm, Nathalie Strutz-Seebohm, Julian A Schreiber
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology August 30, 2024 DOI: 10.33594/000000722 (opens in new tab) via PubMed
Summary
AI-generated from the abstractHuman SK-N-SH cells, both non-differentiated and differentiated, express GluN1 and GluN2B subunits of the NMDA receptor. Exposure to 50 mM (S)-glutamate caused an immediate decrease in cell survival. The unselective NMDA receptor blocker ketamine protected differentiated cells against this toxicity, whereas the GluN2B-selective inhibitor WMS14-10 did not significantly increase cell survival. Higher differentiation levels increased sensitivity to (S)-glutamate-mediated cytotoxicity, which is only partially driven by NMDA receptor overstimulation. Unselective NMDA receptor inhibition can partially reverse (S)-glutamate-induced toxicity, suggesting that SK-N-SH cells are a limited model for studying NMDA receptor-mediated neurodegeneration.
Study at a glance
| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Human SK-N-SH cells |
| Interventions | ketamine WMS14-10 |
| Dose | 50 mM (S)-glutamate |
| Keywords | Neurotoxicity neurotoxic effects Neural toxicity Nerve cell damage Alzheimer disease Ad |
| Citations | 2 |
| Key finding | Unselective NMDA receptor blocker ketamine, but not the GluN2B-selective inhibitor WMS14-10, partially protected differentiated SK-N-SH cells from (S)-glutamate-induced cytotoxicity. |
Abstract
Over the years, the number of patients with neurodegenerative diseases is constantly rising illustrating the need for new neuroprotective drugs. A promising treatment approach is the reduction of excitotoxicity induced by rising (S)-glutamate levels and subsequent NMDA receptor overactivation. To facilitate the search for new NMDA receptor inhibitors neuronal cell models are needed. In this study, we evaluated the suitability of human SK-N-SH cells to serve as a cell model for neurodegeneration induced by NMDA receptor overstimulation. The cytoprotective effect of the unselective NMDA receptor blocker ketamine as well as the GluN2B-selective inhibitor WMS14-10 was evaluated utilizing different cell viability assays, such as endpoint (LDH, CCK-8, DAPI/FACS) and time dependent methods (bioimpedance). Non-differentiated as well as differentiated SK-N-SH cells express GluN1 and GluN2B subunits. Furthermore, 50 mM (S)-glutamate led to an instantaneous decrease in cell survival. Only application of unselective channel blocker ketamine could protect differentiated cells against this effect, while the selective inhibitor WMS14-10 did not significantly increase cell survival. SK-N-SH cells show an increased sensitivity to (S)-glutamate mediated cytotoxicity with higher differentiation level, that is only partially induced by NMDA receptor overstimulation. Furthermore, we showed that only unselective NMDA receptor inhibition can partially reverse (S)-glutamate-induced toxicity.