Migraine is one of the most incapacitating conditions, affecting one in every seven persons and posing a significant social and economic cost. Several studies have found that migraine is a condition that affects a broad area of the central nervous system and is defined by a systemic failure in sensory information processing and integration that occurs even between migraine episodes (interictal period). Patients with migraine, for example, have enhanced cerebral reactions to sensory inputs during the interictal interval. At the moment, the biological processes causing these changes are mainly unclear.
A team of neuroscientists led by Mirko Santello at the University of Zurich’s Institute of Pharmacology and Toxicology, in conjunction with the University of Padua, has found a novel mechanism linked in a rare form of migraine caused by genetic mutation. They claim that this familial hemiplegic migraine type 2 (FHM2) causes astrocytes in the cingulate cortex, a brain area implicated in pain perception, to fail. Astrocytes, or star-shaped brain cells, are critical contributors to neuronal function and have a significant influence on brain circuits and behaviour.
“Despite their abundance, astrocytes have been relatively overlooked by neuroscientists,” says Mirko Santello, last author of the study. Nonetheless, these cells are critical in clearing neurotransmitters. The researchers were able to demonstrate that in familial migraine, astrocytes are unable to eliminate excessive transmitters generated by neurons.
“The impairment in astrocytic glutamate uptake in the cingulate cortex strongly enhances cortical dendritic excitability and thus enhances firing of the neurons,” Santello says. Furthermore, the study found that cingulate brain dysfunction impacts migraine incidence. The researchers demonstrated greater sensitivity to head pain triggers in a mouse model.
“By manipulating astrocytes in the cingulate cortex, we were able to reverse their dysfunction. This prevented an increase in head pain in mice carrying the genetic defect,” says Jennifer Romanos, first author of the study. Migraine is a complex neurological illness that affects a portion of the nerve system.
“Our results provide a clear example of how astrocyte dysfunction produced by a genetic defect affects neuronal activity and sensitivity to head pain triggers,” explains Mirko Santello. The findings contribute to a better understanding of migraine pathogenesis and imply that the cingulate cortex is a major hub in the condition. The discovery of a relationship between astrocyte malfunction in the cingulate cortex and familial migraine may aid in the development of novel migraine treatment techniques.
