Genetic malfunction of brain astrocytes triggers migraine

Neuroscientist of the University of Zurich shed a new light on the mechanisms responsible for familial migraine: They show that a genetic dysfunction in specific brain cells of the cingulate cortex area strongly influences head pain occurrence.
by Annahar Staff

11 July 2020 | 10:56

Source: by Annahar

  • by Annahar Staff
  • Source: Annahar
  • Last update: 11 July 2020 | 10:56

Representative picture. (Steve Heap/Shutterstock.com)

Migraine is one of the most disabling disorders, affecting one in seven people and causing a tremendous social and economic burden. Several findings suggest that migraine is a disease affecting a large part of the central nervous system and characterized by a global dysfunction in sensory information processing and integration, which also occurs between migraine episodes (interictal period). For example, patients with migraine exhibit increased cortical responses to sensory stimuli during the interictal period. At present, the cellular mechanisms responsible for these alterations are largely unknown.

Malfunction of astrocytes in the cingulate cortex

A Lebanese Neuroscientist in the team of Dr. Mirko Santello at the Institute of Pharmacology and Toxicology of the University of Zurich, in collaboration with the University of Padua, has identified a new mechanism implicated in a special form of migraine caused by genetic mutation. The team report that this familial hemiplegic migraine type 2 (FHM2) causes a malfunction of astrocytes in the cingulate cortex, a brain region that is involved in the feeling of pain. Astrocytes, specific star-shaped brain cells, are essential contributors to neuronal function and have a strong impact on brain circuits and behavior.

“Despite their abundance, astrocytes have been relatively overlooked by neuroscientists,” says Mirko Santello, last author of the study. Yet these cells are extremely important to clear transmitters released by neurons. In their study the researchers were able to show that in familial migraine the astrocytes cannot remove excessive transmitters released 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.

Less migraine occurrence due to genetic manipulations

Furthermore, the study reported that the malfunction of the cingulate cortex also influences migraine occurrence. In a mouse model the researchers showed that the mice displayed increased sensitivity to head pain triggers.

“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 complicated disorder that affects part of the nervous 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 Romanos. The findings help to better understand migraine pathophysiology and suggest that the cingulate cortex may represent a critical hub in the disease. The demonstration of the link between dysfunction of astrocytes in the cingulate cortex and familial migraine could help in devising new migraine treatment strategies.

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Jennifer Romanos, lead researcher, is of Lebanese origins. She grew up in Edde-Jbeil and completed a bachelor degree in Life and Earth Sciences at the Lebanese University in Fanar. She moved to France in 2013 to do her Masters at the Ecole Normale Superieure in Lyon. During that time, she had the opportunity to join several research teams at Harvard Medical School and at the Neuroscience Center in Lyon. These research stays increased her interest and passion for understanding neurological disorders and thus, made her decide to pursue a PhD with Dr. Mirko Santello at the Institute of Pharmacology and Toxicology at the University of Zurich. She joined Mirko’s team in 2016 and started working on cortical mechanisms underlying migraine pathology (the third most common disease in the world). Her work specifically focused on the role of astrocytes in cranial pain development.

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