We investigated the effect of intermittent hypoxia, mimicking sleep apnea, on axonal integrity, blood-brain barrier permeability, and cognitive function of mice. Forty-seven C57BL mice were exposed to intermittent or sham hypoxia, alternating 30s of progressive hypoxia and 30s of reoxigenation, during 8h/day. The axonal integrity in cerebellum was evaluated by transmission electron microscopy. Short- and long-term memories were assessed by novel object recognition test. The levels of endothelin-1 were measured by ELISA. Blood-brain barrier permeability was quantified by Evans Blue dye. After 14 days, animals exposed to intermittent hypoxia showed hypomyelination in cerebellum white matter and higher serum levels of endothelin-1. The short and long-term memories in novel object recognition test was impaired in the group exposed to intermittent hypoxia as compared to controls. Blood-brain barrier permeability was similar between the groups. These results indicated that hypomyelination and impairment of short- and long-term working memories occurred in C57BL mice after 14 days of intermittent hypoxia mimicking sleep apnea.
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http://dx.doi.org/10.1016/j.brainres.2014.11.052 | DOI Listing |
Alzheimers Dement
January 2025
Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Xicheng District, Beijing, China.
Alzheimer's disease (AD) is a degenerative disease characterized by progressive cognitive dysfunction. The strong link between nutrition and the occurrence and progression of AD pathology has been well documented. Poor nutritional status accelerates AD progress by potentially aggravating amyloid beta (Aβ) and tau deposition, exacerbating oxidative stress response, modulating the microbiota-gut-brain axis, and disrupting blood-brain barrier function.
View Article and Find Full Text PDFJ Extracell Vesicles
January 2025
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Extracellular vesicles (EVs) from brain-seeking breast cancer cells (Br-EVs) breach the blood-brain barrier (BBB) via transcytosis and promote brain metastasis. Here, we defined the mechanisms by which Br-EVs modulate brain endothelial cell (BEC) dynamics to facilitate their BBB transcytosis. BEC treated with Br-EVs show significant downregulation of Rab11fip2, known to promote vesicle recycling to the plasma membrane and significant upregulation of Rab11fip3 and Rab11fip5, which support structural stability of the endosomal compartment and facilitate vesicle recycling and transcytosis, respectively.
View Article and Find Full Text PDFCerebrovascular endothelial cell (EC) subtypes characterized by blood-brain barrier (BBB) properties or fenestrated pores are essential components of brain-blood interfaces, supporting brain function and homeostasis. To date, the origins and developmental mechanisms underlying this heterogeneous EC network remain largely unclear. Using single-cell-resolution lineage tracing in zebrafish, we discover a multipotent vascular niche at embryonic capillary borders that generates ECs with BBB or fenestrated molecular identity.
View Article and Find Full Text PDFPeptides play critical roles in cellular functions such as signaling and immune regulation, and peptide-based biotherapeutics show great promise for treating various diseases. Among these, cell-penetrating peptides (CPPs) are particularly valuable for drug delivery due to their ability to cross cell membranes. However, the mechanisms underlying CPP-mediated transport, especially across the blood-brain barrier (BBB), remain poorly understood.
View Article and Find Full Text PDFChem Sci
January 2025
Department of Chemistry, Imperial College London Molecular Sciences Research Hub, 82 Wood Lane, White City Campus London W12 0BZ UK
The blood-brain-barrier prevents many imaging agents and therapeutics from being delivered to the brain that could fight central nervous system diseases such as Alzheimer's disease and strokes. However, techniques such as the use of stapled peptides or peptide shuttles may allow payloads through, with bioconjugation achieved bio-orthogonal tetrazine/norbornene click chemistry. A series of lanthanide-tetrazine probes have been synthesised herein which could be utilised in bio-orthogonal click chemistry with peptide-based delivery systems to deliver MRI agents through the blood-brain-barrier.
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