Effect of altered production and storage of dopamine on development and behavior inC. elegans

Abstract

The nematode,Caenorhabditis elegans, is an advantageous model for studying developmental toxicology due to its homology to humans and well-defined developmental stages. Similarly to humans,C. elegansutilize dopamine as a neurotransmitter to regulate motor behavior. We have previously reported behavioral deficits in a genetic model ofC. elegans(OK411) that lack the neurotransmitter transporter necessary for packaging dopamine into synaptic vesicles. Anecdotally, we observed theseC. elegansappeared to have a smaller body size, which is supported by prior studies that observed a larger body size inC. elegansthat lack the enzyme that catalyzes dopamine synthesis, suggesting a complex regulatory system in which dopamine mediates body size inC. elegans. However, the question of whether body size abnormalities apparent inC. eleganswith disruptions to their dopamine system are developmental or purely based on body size remains unanswered. Here, we present data characterizing the effect of gene mutations in dopamine-related proteins on body size, development, and behavior. We analyzedC. elegansthat lack the ability to sequester dopamine (OK411), that overproduce dopamine (UA57), and a novel strain (MBIA) generated through crossing OK411 and UA57, which lacks the ability to sequester dopamine into vesicles and additionally endogenously overproduces dopamine. This novel strain was generated to address the hypothesis that an endogenous increase in production of dopamine can rescue deficits caused by a lack of vesicular dopamine sequestration. Compared to wild type, OK411 have shorter body lengths and behavioral deficits in early life stages. In contrast, the MBIA strain have similar body lengths to wild-type by early adulthood and display similar behavior to wild-type by early adulthood. Our data suggests that endogenously increasing the production of dopamine is able to mitigate deficits inC. eleganslacking the ability to package dopamine into synaptic vesicles. These results provide evidence that the dopamine system impacts development, growth, and reproduction inC. elegans.