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)
Study at a glance
AI-extracted from the abstract| 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 Gluta |
| Citations | 2 |
| Key points | 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.