FINAL REPORT: The Role of Ionotropic Glutamate Receptor Genes in Migraine

Read the manuscript of Dr. Esposito’s research.

Summary

Glutamate is the principal excitatory neurotransmitter in the central nervous system and is widely accepted as playing a major role in the pathophysiology of migraine. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could, therefore, be considered potential candidates for causing/predisposing migraine when mutated.

To investigate this, we compared 35 glutamate receptor gene variants between migraineurs and controls and found three variants strongly associated with migraine with aura, and another variant which was associated with migraine without aura. This study represents the first genetic evidence of a link between glutamate receptors and migraine.

Hypothesis vs. Findings

The goal of the project was to determine whether glutamate receptors are responsible for a susceptibility to migraine. That goal was met. We showed that variants in glutamate receptor genes are associated with migraine. Moreover, we demonstrated that at risk variants may affect the expression of glutamate receptor genes, which consequently modulate the individual’s susceptibility to migraine. Unfortunately, the cellular model that we developed for electrophysiological study did not enable us to observe differences in calcium levels.

Unanswered Questions

The most important question generated by our research is whether medications that target different types of glutamate receptors could represent a novel treatment for migraine.  Answering this question with further basic and clinical studies will have substantial implications for the field of migraine and for migraine patients.

What this Research Means to You

Targeting different types of glutamate receptors might represent a new treatment approach for migraine medications.