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The role of pericytic laminin in blood brain barrier integrity maintenance
- Source :
- Scientific Reports
- Publication Year :
- 2016
-
Abstract
- Laminin, a major component of the basement membrane, plays an important role in blood brain barrier regulation. At the neurovascular unit, brain endothelial cells, astrocytes, and pericytes synthesize and deposit different laminin isoforms into the basement membrane. It has been shown that laminin α4 (endothelial laminin) regulates vascular integrity at embryonic/neonatal stage, while astrocytic laminin maintains vascular integrity in adulthood. Here, we investigate the function of pericyte-derived laminin in vascular integrity. Using a conditional knockout mouse line, we report that loss of pericytic laminin leads to hydrocephalus and BBB breakdown in a small percentage (10.7%) of the mutants. Interestingly, BBB disruption always goes hand-in-hand with hydrocephalus in these mutants, and neither symptom is observed in the rest 89.3% of the mutants. Further mechanistic studies show that reduced tight junction proteins, diminished AQP4 expression, and decreased pericyte coverage are responsible for the BBB disruption. Together, these data suggest that pericyte-derived laminin is involved in the maintenance of BBB integrity and regulation of ventricular size/development.
- Subjects :
- 0301 basic medicine
Blood–brain barrier
Article
Desmin
Receptor, Platelet-Derived Growth Factor beta
03 medical and health sciences
Mice
0302 clinical medicine
Laminin
Conditional gene knockout
medicine
Animals
Receptor
Cells, Cultured
Basement membrane
Aquaporin 4
Mice, Knockout
Multidisciplinary
Microscopy, Confocal
Tight Junction Proteins
Tight junction
biology
Chemistry
Brain
Cell biology
Mice, Inbred C57BL
Microscopy, Electron
030104 developmental biology
medicine.anatomical_structure
Phenotype
Blood-Brain Barrier
Astrocytes
biology.protein
Pericytes
030217 neurology & neurosurgery
Hydrocephalus
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....918fecb82220ad3f649a6c5cf186a6c4