Glucose promotes neuron morphology abnormalities and egg-laying defects dependent of the serotonin signaling pathway in Caenorhabditis elegans

A chronic hyperglycemic state can lead to neuropathological complications such as permanent nerve damage. Neuropathology is a debilitating ailment that affects nearly half of the individuals with diabetes, underscoring the relevance to investigate the impact of diet and glucose levels on the nervous system. Using the genetic model system Caenorhabditis elegans , we determined that a diet rich in glucose impacts biological processes dependent on neuronal function. The rate of intrauterine egg-hatching increased in animals fed a glucose diet and the inhibition of dopamine or serotonin is sufficient to counteract the impact of the glucose diet. The glucose-induced intrauterine egg-hatching phenotype is independent of the SER-1 and SER-7 receptors yet dependent on the DAF16/FOXO transcription factor. Furthermore, animals fed a glucose-supplemented diet displayed abnormal morphologies in the HSN and NSM serotonergic neurons and the HSN displayed axonal degeneration, which is a prominent pathological feature in neurological dysfunction and disease. Combined these data indicate that a glucose-diet affects nervous system and signaling pathways in C. elegans , which can be used to further model diet-induced neuropathy.