Abstract
Glutamatergic signaling via N-methyl-D-aspartate receptors (NMDARs) is important for physiological functioning, but can also induce cell death via excitotoxic mechanisms in many neuropathological diseases, such as stroke. Altering the cellular response to excitotoxic insults by modulating the downstream effects of NMDAR activation represents a promising therapeutic approach. For example, α7 nicotinic acetylcholine receptors (α7 nAChRs) signaling has been shown to be able to change NMDA-induced neurotoxicity in some models. However, both neuroprotective and neurotoxic effects have been reported. In this study, we examined the effect of co-activation of α7 nAChRs on NMDA-mediated cell death in rat organotypic hippocampal slice cultures (OHSCs). Our results show that α7 nAChR stimulation did not significantly influence NMDA-induced excitotoxic cell damage as measured by propidium iodide uptake. However, treatment of OHSCs with the α7 nAChR agonist choline alone induced an increase in the propidium iodide signal. Both the α7 nAChR antagonist methyllycaconitine (MLA) and the NMDAR antagonist (RS)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) were able to block this effect in the dentate gyrus and hippocampal subfield CA3.
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The authors thank Ms. Debra MacDonald for technical assistance.
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DFH was the recipient of the Innovation PEI Graduate Student Award and the Dr. Regis Duffy Graduate Scholarship in Science. Research funding was provided by an AVC Internal Research grant.
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Happ, D.F., Tasker, R. Effects of α7 Nicotinic Receptor Activation on Cell Survival in Rat Organotypic Hippocampal Slice Cultures. Neurotox Res 33, 887–895 (2018). https://doi.org/10.1007/s12640-017-9854-2
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DOI: https://doi.org/10.1007/s12640-017-9854-2