Search bioRxiv⌕ Search

Biology subjects

Carecho, R.

Publications and source records attributed to Carecho, R..

2 recordsLinked to original sources

From berries to brain: Assessing the impact of (poly)phenols in the MPTP mouse model of Parkinson's disease

The growing burden of chronic neurodegenerative diseases (NDs), particularly Parkinsons disease (PD), prompts the need for effective preventive strategies and treatments. Dietary (poly)phenols have emerged for their neuroprotective potential. This study investigated a (poly)phenol-enriched diet, comprising a berry mixture, to counteract key PD hallmarks in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice and elucidate the phenolic metabolic fingerprint underlying these effects. The berry-enriched diet prevented motor deficits in the MPTP mice model, preserved dopaminergic neurons in the midbrain, reduced glial activation and gene expression of inflammatory cytokines. Notably, berries also attenuated macrophage infiltration observed in the substantia nigra 7 days post-MPTP. Metabolomic analysis revealed distinct phenolic signatures in plasma and brain tissue between standard- and berry-fed mice. Overall, this pioneering study provides compelling evidence that a (poly)phenol-enriched diet may play a protective role in neurodegenerative disorders, highlighting its potential for future strategies to prevent or slow PD progression.

neuroscience↗

Circulating (poly)phenol metabolites in the brain: unveiling in vitro and in vivo blood-brain barrier transport

Circulating metabolites resulting from colonic metabolism of dietary (poly)phenols are highly abundant in the bloodstream, though still marginally explored, particularly concerning their brain accessibility. Our goal is to disclose (poly)phenol metabolites blood-brain barrier (BBB) transport, in vivo and in vitro, as well as their role at BBB level. For three selected metabolites, benzene-1,2-diol-3-sulfate/benzene-1,3-diol-2-sulfate (pyrogallol-sulfate - Pyr-sulf), benzene-1,3-diol-6-sulfate (phloroglucinol-sulfate - Phlosulf), and phenol-3-sulfate (resorcinol-sulfate - Res-sulf), BBB transport was assessed in human brain microvascular endothelial cells (HBMEC). Their potential in modulating in vitro BBB properties at circulating concentrations was also studied. Metabolites fate towards the brain, liver, kidney, urine, and blood was disclosed in Wistar rats upon injection. Transport kinetics in HBMEC highlighted different BBB permeability rates, where Pyr-sulf emerged as the most in vitro BBB permeable metabolite. Pyr-sulf was also the most potent regarding BBB properties improvement, namely increased beta({beta})-catenin membrane expression and reduction of zonula occludens-1 membrane gaps. Whereas no differences were observed for transferrin, increased expression of caveolin-1 upon Pyr-sulf and Res-sulf treatments was found. Pyrsulf was also capable of modulating gene and protein expression of some solute carrier transporters. Notably, each of the injected metabolites exhibited a unique tissue distribution in vivo, with the remarkable ability to almost immediately reach the brain.

biochemistry↗