High-salt diet suppresses autoimmune demyelination by regulating the blood–brain barrier permeability, 2021 Shin-Young Na et al

Mij · Mar 22, 2021

Abstract
Sodium chloride, “salt,” is an essential component of daily food and vitally contributes to the body’s homeostasis. However, excessive salt intake has often been held responsible for numerous health risks associated with the cardiovascular system and kidney. Recent reports linked a high-salt diet (HSD) to the exacerbation of artificially induced central nervous system (CNS) autoimmune pathology through changes in microbiota and enhanced TH17 cell differentiation [M. Kleinewietfeld et al., Nature 496, 518–522 (2013); C. Wu et al., Nature 496, 513–517 (2013); N. Wilck et al., Nature 551, 585–589 (2017)]. However, there is no evidence that dietary salt promotes or worsens a spontaneous autoimmune disease. Here we show that HSD suppresses autoimmune disease development in a mouse model of spontaneous CNS autoimmunity. We found that HSD consumption increased the circulating serum levels of the glucocorticoid hormone corticosterone. Corticosterone enhanced the expression of tight junction molecules on the brain endothelial cells and promoted the tightening of the blood–brain barrier (BBB) thereby controlling the entry of inflammatory T cells into the CNS. Our results demonstrate the multifaceted and potentially beneficial effects of moderately increased salt consumption in CNS autoimmunity.

multiple sclerosis

dietary salt

experimental autoimmune encephalomyelitis

Excess salt (sodium chloride; NaCl) intake is associated with elevated blood pressure. However, the optimal range of sodium intake for cardiovascular health is controversial. A drastic reduction of salt intake is widely considered as a logical therapeutic consequence (4), a stand, which has not been met with unreserved acclaim (5).

Dietary salt intake has also been considered as an important risk factor for autoimmune diseases like multiple sclerosis (MS), whose incidence is steadily increasing in the last few decades. However, evidence that sodium intake is directly associated with MS pathogenesis is controversial (6, 7). Previous reports found that in actively induced experimental autoimmune encephalomyelitis (active EAE), a mouse model of MS, a high-salt diet (HSD) drives T cell differentiation toward proinflammatory pathogenic TH17 cells and exacerbates clinical disease (1 ⇓–3). It is important to note that the active EAE model used in these studies substantially differs from MS in regards to the disease initiation phase. Indeed, active EAE is induced by immunization with autoantigen and immune-activating microbial adjuvants (complete Freund’s adjuvant [CFA] plus pertussis toxin). This protocol allows simultaneous activation and expansion of naïve T cells and the opening of the blood–brain barrier (BBB) by pertussis toxin to facilitate the entry of activated T cells into the central nervous system (CNS). However, similar processes of T cell activation or the opening of the BBB through immunization are unknown in MS patients. In fact, vaccination against tetanus, hepatitis B, or influenza does not correlate with the onset of MS, or with relapses of the disease (8).

Here, we evaluated the effects of an HSD on early pathogenic events that are necessary for the initiation of CNS autoimmunity using a spontaneous EAE mouse model. Against expectation, an HSD profoundly protected spontaneous EAE development. High salt altered the hormonal balance by interfering with the metabolism of corticosterone. The increased corticosterone levels induced the higher expression of BBB tight junction molecules to limit the infiltration of immune cells into the CNS. Collectively, our data suggest that moderate elevation of salt uptake might be beneficial in CNS autoimmunity.
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https://www.pnas.org/content/118/12/e2025944118

MeSci · Mar 22, 2021

Pointless using mice. What a shame - I'm interested in this. Shame for the poor mice too - they are almost certainly killed, as the vast majority of lab animals are.

Peter Trewhitt · Mar 22, 2021

MeSci said: ↑

Pointless using mice. What a shame - I'm interested in this. Shame for the poor mice too - they are almost certainly killed, as the vast majority of lab animals are.
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It used to be a condition of the Home Office licences for animal research here in the UK that the animals were destroyed at the end of their research usefulness, I don’t know if that continues to be the case now. This, at least in the past, meant after the main research was done, that more harmful research such as looking at the effects of very high drug dosages was undertaken as the animal subjects were going to be killed any way.

Mij · Mar 22, 2021

I watched a program several months ago about growing cultured human cells on scaffolds embedded on plastic chips, forming tiny structures that mimic the functioning of our heart, liver, kidneys and lungs. These could provide a novel way to test the effects of new compounds or drugs on human cells.

borko2100 · Mar 23, 2021

It is quite likely that the blood brain barrier may be involved in the pathophysiologically of ME in some way. Many sufferers (me included) report aquiring new food intolerances as their illness progresses over the years. Me for example, for decades I never had issues with MSG and Capsaicin. But a few years ago I started experiencing very strange neurological symptoms every time I ingest them. Maybe it is because a compromised blood brain barrier allows more of them to enter the brain?

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High-salt diet suppresses autoimmune demyelination by regulating the blood–brain barrier permeability, 2021 Shin-Young Na et al

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