The Powerhouse of Depression: The Impact of MTCH‐1 Deficiency on Reward Signaling in C. Elegans

Abstract

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. One of MDD’s most troubling symptoms is the loss of reward firing, or anhedonia. Current publications indicate that MTCH‐2, a gene involved with mitochondrial transport, is related to a decrease in firing rates in the hippocampus of mice. Additionally, a GWAS reported an association between MTCH‐2 and neuroticism in humans. Consequently, we hypothesize that a MTCH‐2 related decrease in firing rates in the nucleus accumbens could potentially play a role in the development of depressive symptoms.The C. elegans MTCH‐1 protein shows an 87% homology to the human MTCH‐2 protein. Here, we examine the relationship between the MTCH‐1 gene, a previously unexamined gene, and C. Elegans reward firing. Because C. elegans reward firing levels have been associated with varying speed change fluidity in past studies, we measure C. elegans motility as a proxy for reward firing.In this study, we compare motility and gene expression between MTCH‐1 deficient worms and wildtype worms. We are using WormTracker to quantify motility based upon turn count in videos of worms recorded on ToupCam. Post all motility tests, a PCR and GFP assay on worms serve to verify their phenotypes. After our assays are concluded, we plan to use ANOVA for statistical analysis of our results. Thus, together, these data may demonstrate the influence of MTCH‐2 on reward firing, providing new insights into indicators and treatments of depression.Support or Funding InformationThis work was supported and funded by the Nueva School. The Shen Lab at Stanford University provided lab equipment and N2 worms. Worms and technical support were provided by Caenorhabditis Genetics Center (CGC) ‐ College of Biological Sciences.