Investigating the Effect of SER-1 in a Caenorhabditis elegans Model of Glutamate Excitotoxicity
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Excitotoxicity, the underlying mechanism common to all neurodegenerative diseases, is the pathology of necrotic effects caused by the prolonged activation of excitatory neurotransmitter receptors in the central nervous system. Glutamate is the most widely investigated neurotransmitter with respect to excitotoxicity. Of the two major classes of glutamate receptors, the direct antagonism of ionotropic glutamate receptors has shown to be neuroprotective. However, prolonged antagonism of these receptors also leads to neuronal loss. Thus, there is significant need for alternative targets. Serotonergic neurotransmission has been shown to modulate glutamate excitotoxicity; however, not much work has been done to assess the viability of serotonin receptors as neuroprotective targets for glutamate excitotoxicity. This study investigates the role of SER-1 in the glutamate excitotoxicity Caenorhabditis elegans (C. elegans) model ZB1102. By examining the number of necrotic neurons, locomotor activity, and lifespan in excitotoxicity models of C. elegans, our results suggest that SER-1 knock out animals have reduced instances of neuronal death, showing neuroprotective effects at the cellular level. However, our behavior assays indicate that serotonergic transmission is more complex with respect to excitotoxicity and does not show that loss of SER-1 has sufficient neuroprotective effects in C. elegan locomotion or lifespan. These findings suggest that the development of serotonin receptors antagonists may be beneficial in modulating glutamate excitotoxicity and motivate the further investigation in C. elegan models.