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Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, Buendia I, Santisteban MM, Segarra SG, Koizumi K, Sugiyama Y, Murphy M, Voss H, Anrather J, Iadecola C. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018 Feb;21(2):240-249. Epub 2018 Jan 15 PubMed.
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University of Southern California
This is a very important paper showing the mechanism underlying the link between dietary salt and cognitive function through endothelial-mediated regulation of cerebral blood flow responses. In an elegant series of experiments, Dr. Iadecola’s team has convincingly shown that salt acts by affecting TH17 cell in the small intestine causing IL17 production, which in turn blocks NO generation by brain endothelial cells, leading to dysregulated blood flow responses to brain activation that can set a stage for development of neurodegenerative changes and behavioral deficits. To my knowledge this is first mechanistic study explaining the effect of salt on loss of endothelial-mediated vasodilation of brain vessels through inhibition of the NO system via very complex peripheral mechanism involving cross-talk of peripheral gut-derived immune TH17 cells with endothelial cells of cerebral blood vessels.
View all comments by Berislav ZlokovicUniversity of South Florida
This is an interesting study that investigated the effect of high-salt diet on alteration of blood-circulation parameters. The authors have shown that high-salt diet alters cerebral blood flow (CBF), increases plasma interleukin 17 (IL-17) and causes endothelial damage. Others, including us, have shown the effect of high salt diet on CBF as well as core blood pressure in animal models (Taheri et al., 2016). However, the results of such studies are controversial as they depend on the experimental settings, such as the number of animals, diet composition, diet regimen, the CBF measurement methods, and the statistical inference powers. To overcome these controversies more studies with a higher number of animals and more advanced CBF measurement methods are needed.
Exploring the mechanism by which a high-salt diet regimen affects endothelial cells function is a strong part of this report. Many pathways have been suggested by which high-salt diet can affect blood circulation and endothelial dysfunction, including Na/Ca channels and NO. Alteration of NO synthesis was long thought to be the main culprit of cerebral endothelial dysfunction and cerebral hypoperfusion. However, its connection to high salt diet and gut cells is very interesting.
References:
Taheri S, Yu J, Zhu H, Kindy MS. High-Sodium Diet Has Opposing Effects on Mean Arterial Blood Pressure and Cerebral Perfusion in a Transgenic Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2016 Oct 4;54(3):1061-1072. PubMed.
View all comments by Saeid TaheriMake a Comment
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