The Neuroprotective Effects of RS-127445 in a Glutamate Excitotoxicity Model of Caenorhabditis elegans
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Neurodegenerative diseases affecting the central nervous system are characterized by neuronal impairment or death. One mechanism leading to neuronal death in many neurodegenerative diseases is glutamate excitotoxicity. Glutamate excitotoxicity is formally defined as the death of neurons resulting from the overstimulation of glutamate receptors. Antagonism of glutamate receptors has not shown the desired results; thus, alternative strategies are needed to mediate glutamate excitotoxicity. One alternative approach to reduce glutamate excitotoxicity may be the modulation of serotonin (5-HT) receptors. In this study we investigated the neuroprotective effect of RS-127445, a 5-HT receptor antagonist, in a C. elegans glutamate excitotoxicity model. To measure the effects of the drug treatment, two assays were conducted: 1) differential interference contrast (DIC) microscopy was used to count the number of necrotic neurons per animal and 2) the animal’s lifespan was measured. Lifespan assay results were inconclusive and showed significant variability among experimental groups; however, the DIC microscopy data shows that RS-127445 at 2.0 mM significantly reduces the number of necrotic neurons in the excitotoxicity model. The results from this study demonstrate that antagonism of 5-HT receptors has neuroprotective effects in a C. elegans glutamate excitotoxicity model.