Scientists have made a groundbreaking discovery about the role of the glycocalyx layer in maintaining brain health. The study found that dysregulation of this critical sugar-rich layer accelerates aging and disease, providing a new therapeutic target for restoring brain health.
The blood-brain barrier (BBB) plays a crucial role in supporting brain function by regulating the exchange of nutrients and waste products between the brain and bloodstream. The glycocalyx layer, which coats the BBB’s luminal surface, is essential for maintaining its integrity.
Researchers used transmission electron microscopy and lanthanum nitrate staining to visualize the glycocalyx layers in young and aged mice. They found that significantly fewer luminal glycocalyx layers existed in aged mice compared to young mice, leading to decreased glycocalyx area and thickness. The reduction was particularly pronounced in the brain.
The study also revealed significant dysregulation of glycosylation-related genes with aging, including downregulation of mucin-type O-glycan biosynthesis genes and upregulation of heparan sulfate metabolism genes. This suggests that impaired mucin-type O-glycosylation plays a key role in BBB dysfunction.
Further research showed that the loss of mucin-type O-glycan biosynthesis enzymes led to increased BBB permeability, extensive leakage of immunoglobulin G and albumin into the brain, and susceptibility to cerebral hemorrhaging. Conversely, overexpressing these enzymes improved BBB function, reduced neuroinflammation, and enhanced cognitive performance.
The study’s findings suggest that restoring the glycocalyx layer may help prevent BBB breakdown, mitigate neurodegeneration, and improve cognitive resilience in aging populations. This breakthrough discovery offers new hope for the development of therapeutic strategies to target the underlying molecular mechanisms driving age-related CNS diseases.
Source: https://www.news-medical.net/news/20250227/Scientists-uncover-how-a-sugar-shield-in-brain-blood-vessels-protects-against-aging-and-disease.aspx