Author response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
RogelioLeira, PhD, MD, Hospital Clínico Universitario de Santiago de Compostela
ClaraDomínguez, MD, Hospital Clínico Universitario de Santiago de Compostela
Submitted April 13, 2019
We are grateful for Dr. Shubhakaran’s valuable comment on our article; we agree that the mechanisms underlying the role of iron in migraine need further investigation.
In our study,1 we hypothesized a role of inflammation in iron deposition and analyzed several local mechanisms that could be involved in this process. Enlargement of iron deposits has been reported in other neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis or Alzheimer disease.2
Iron is essential in the brain for ATP production, cholesterol and fatty acid synthesis involved in myelinization, and neurotransmitter metabolism. The way iron is released to the brain depends on a highly regulated transcellular pathway acting in endothelial cells and microglia.3 Endothelial cells regulate iron trafficking through hepcidine and expression of transferrin receptors; they also contain relatively high amounts of ferritin, serving as active reservoirs of iron. Regarding microglia,4 it requires iron as a cofactor. Increased cytokine levels can cause iron intracellular sequestration—an effect mediated also by ferritin.
Current knowledge points to local mechanisms as key for brain iron accumulation; however, further investigation is needed on the role of systemic iron and ferritin levels, iron intake and iron transporters on migraine, and migraine chronification.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Domínguez C, López A, Ramos-Cabrer P, et al. Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine. Neurology 2019;92:e1076–e1085.
Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L. The role of iron in brain aging and neurodegenerative disorders. Lancet Neurol 2014;13:1045–1060.
Nnah IC, Wessling-Resnick M. Brain Iron Homeostasis: A Focus on Microglial Iron. Pharmaceuticals (Basel) 2018;11:1–14.
McCarthy RC, Sosa JC, Gardeck AM, Baez AS, Lee CH, Wessling-Resnick M. Inflammation-induced iron transport and metabolism by brain microglia. J Biol Chem 2018;293:7853–7863.
We are grateful for Dr. Shubhakaran’s valuable comment on our article; we agree that the mechanisms underlying the role of iron in migraine need further investigation.
In our study,1 we hypothesized a role of inflammation in iron deposition and analyzed several local mechanisms that could be involved in this process. Enlargement of iron deposits has been reported in other neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis or Alzheimer disease.2
Iron is essential in the brain for ATP production, cholesterol and fatty acid synthesis involved in myelinization, and neurotransmitter metabolism. The way iron is released to the brain depends on a highly regulated transcellular pathway acting in endothelial cells and microglia.3 Endothelial cells regulate iron trafficking through hepcidine and expression of transferrin receptors; they also contain relatively high amounts of ferritin, serving as active reservoirs of iron. Regarding microglia,4 it requires iron as a cofactor. Increased cytokine levels can cause iron intracellular sequestration—an effect mediated also by ferritin.
Current knowledge points to local mechanisms as key for brain iron accumulation; however, further investigation is needed on the role of systemic iron and ferritin levels, iron intake and iron transporters on migraine, and migraine chronification.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References