Abstract
A number of studies report that a diet high in protein influences cognitive performance, but the results are inconsistent. Studies demonstrated that protein from different food sources has differential effects on cognition. It is increasingly recognized that the integrity of cerebrovascular blood–brain barrier (BBB) is pivotal for central nervous system function. However, to date, no studies have reported the effects of high-protein diets on BBB integrity. Therefore, in this study, the effects of diets enriched in casein or soy protein on BBB permeability were investigated. Immunomicroscopy analyses of cerebral parenchymal immunoglobulin G extravasation indicated significant BBB disruption in the cortex of young adult mice maintained on high-casein diet for 12 weeks, while no signs of BBB dysfunction were observed in mice fed with control or high-soy protein diet. Moreover, cortical expression of glial fibrillary acidic protein (GFAP) was significantly greater in mice fed the high-casein diet compared to control mice, indicating heightened astrocyte activation, whereas mice maintained on a soy-enriched diet showed no increase of GFAP abundance. Plasma concentrations of homocysteine were markedly greater in mice maintained on a high-casein diet in comparison to control mice. Collectively, these findings suggest that a diet enriched in casein but not soy protein may induce astrocyte activation through exaggerated BBB permeability by increased plasma homocysteine. The outcomes indicate the differential effects of protein sources on BBB and neuroinflammation, which may provide an important implication for dietary guidelines for protein supplementation.
Highlights
The blood–brain barrier (BBB) is a unique feature of the neurovascular unit that physically separates brain from blood
Substantial peri-vascular parenchymal extravasation of plasma-derived immunoglobulin g (IgG) was observed in the mice maintained on a diet enriched in casein for 12 weeks, indicating substantial breakdown of BBB, while no distinct evidence of BBB disruption was found in control and soy protein-fed mice (Figure 1A)
While emerging evidence suggests that BBB integrity may be central to neurocognitive performance, no studies to date examined the effects of high-protein consumption on BBB permeability
Summary
The blood–brain barrier (BBB) is a unique feature of the neurovascular unit that physically separates brain from blood. The plasma membranes of the endothelial cells contain adherens and tight junction proteins that limit the paracellular space between endothelial cells to reinforce strict control of transport of substances between blood and brain compartments [1, 2]. The BBB has recently garnered significant research interest within the area of neurodegenerative disorders. A dysfunctional BBB results in cerebral extravasation of blood-borne neuroactive molecules including pro-inflammatory cytokines and thereafter, potential genesis of reactive oxygen species. Elevated neuroinflammation and oxidative stress can increase endoplasmic reticulum stress, protein misfolding, and DNA and cellular damage, which may eventually result in the loss of neurons [4]
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