Astrocytes are essential cells with multiple functions in the brain and nervous system. In a recent study, scientists have discovered its connection to a mutated form of migraine called familial hemiplegic migraine type 2 (FHM2).
A collaboration between the Institute of Pharmacology and Toxicology of the University of Zurich and the University of Padua have identified what may trigger a mutated migraine called FHM2. Their findings concluded that FHM2 causes astrocytes to malfunction within the brain region associated with pain, the cingulate cortex.
Migraines are strong headaches that may last four hours to three days and more. The disorder is found in one in seven people, affecting over 36 million Americans, affected women thrice as much as men, according to the American Migraine Foundation.
Medical experts do not know the exact causes of migraines, yet have discovered in research that most likely it has to do with changes of blood flow in the brain or that it is genetically passed on. General research also points to an overactive cell sending signals to activate the trigeminal nerve which gives sensation to the head and face. The trigeminal nerve then releases the chemical calcitonin gene-related peptide (CGRP), causing blood vessels in the brain to swell, releasing neurotransmitters associated with inflammation and pain.
Abundant Astrocytes
'Despite their abundance, astrocytes have been relatively overlooked by neuroscientists," says Mirko Santello, who led the research. Astrocytes are star-shaped brain cells with several roles from facilitating neurotransmission, providing neuron nutrients, supporting the blood-brain barrier, and repairing nervous tissue after incurring an injury.
The team found that astrocytes are unable to remove excess glutamate, a type of transmitter which plays a role in learning and memory, in a familial migraine. 'The impairment in astrocytic glutamate uptake in the cingulate cortex strongly enhances cortical dendritic excitability and thus enhances firing of the neurons,' said Santello.
Using a knock-in mouse model, or KI mice used for genetic engineering experiments, the scientists displayed how head pain triggers increases sensitivity, showing that migraine occurrences are influenced by the malfunction of the cingulate cortex. Jennifer Romanos, a co-author in the study, said, '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.'
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Cingulate Cortex and the Nervous System
Their research also sheds light on some complications on how migraines affect the nervous system. Santello explained that their results are an 'example of how astrocyte dysfunction produced by a genetic defect affects neuronal activity and sensitivity to head pain triggers.' Aside from pain, the cingulate cortex is responsible for emotions, processing information, learning, and memory.
Santello and his team better understood the pathophysiology of migraines and that the cingulate cortex may be a critical hub of the disorder. Moreover, when interactions between neurons and astrocytes are disturbed, it causes other types of neurological orders which impact brain circuits and behavior.
Today, migraines are treated by taking pain-relieving medication, preventive medication, and anti-nausea drugs. Discovering the link between dysfunctional astrocytes in the cingulate cortex and FHM2 may help create new migraine drug treatments.
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