Seizure Vulnerability in a C. elegans Obesity Model

Seizure Vulnerability in a C. elegans Obesity Model

Alvin Sherman Library

Metabolic disorders such as diabetes mellitus, characterized by hyperglycemia due to defects in insulin secretion, affect millions of people and increasingly more. Epidemiological studies have shown that individuals with diabetes have a higher risk of developing epilepsy, a neurological disorder where recurrent seizures occur. Conversely, many antiepileptics affect glucose and lipid metabolism.

The nematode Caenorhabditis elegans (C. elegans) is a model organism suited for studying metabolic and neurological disorders, due to its genetic tractability, short life cycle, and conserved signaling pathways. Although previous studies have developed and used genetic and diet-induced obesity models in C. elegans, none have characterized the relationship between seizures and diabetes in these animals. This study takes advantage of the obesogenic models to evaluate the relationship between metabolic profile and seizure susceptibility.

We recently developed a platform for quantifying the degree of electroshock-induced seizures in C. elegans. Using this assay, we report the effect of diabetic obesity on seizures. Animals were acutely or chronically exposed to high glucose diet or alloxan for diet- or drug-induced obesity, respectively. Importantly, our results are the first to evaluate the physiological effects of alloxan—a compound commonly used to induce diabetes in laboratory mammals—for the first time in an invertebrate model. Worms with mutations in daf-16 or daf-2 were used for the genetic model of obesity.

This study will contribute to a better understanding of processes that link diabetes and seizure susceptibility and establish a platform to explore the impact of metabolic dysfunctions on the nervous system.