Abstract
The blood‐brain barrier (BBB) is essential for a functional neurovascular unit. Most studies focused on the cells forming the BBB, but very few studied the basement membrane (BM) of brain capillaries in ageing. We used transmission electron microscopy and electron tomography to investigate the BM of the BBB in ageing C57BL/6J mice. The thickness of the BM of the BBB from 24‐month‐old mice was double as compared with that of 6‐month‐old mice (107 nm vs 56 nm). The aged BBB showed lipid droplets gathering within the BM which further increased its thickness (up to 572 nm) and altered its structure. The lipids appeared to accumulate toward the glial side of the BM. Electron tomography showed that the lipid‐rich BM regions are located in small pockets formed by the end‐feet of astrocytes. These findings suggest an imbalance of the lipid metabolism and that may precede the structural alteration of the BM. These alterations may favour the accretion of abnormal proteins that lead to neurodegeneration in ageing. These findings warrant further investigation of the BM of brain capillaries and of adjoining cells as potential targets for future therapies.
Highlights
The blood‐brain barrier (BBB) controls the molecular composition of the neuronal environment
This study focused on the ultrastructural changes of the BBB in ageing but otherwise healthy C57Bl/6J mice and revealed an unexpected accumulation of lipids in the basement membrane (BM) of brain capillaries which, to our knowledge, was not previously reported
The BM is synthetized by endothelial cells and pericytes, but astrocytes may be involved in BM homeostasis.[17]
Summary
The blood‐brain barrier (BBB) controls the molecular composition of the neuronal environment. In the BBB, the endothelial cell BM encloses the pericytes and tightly attaches the astrocyte foot processes by specific adhesion molecules.[1] The end‐feet of astrocytes overlap and cover almost the entire surface of the BM, forming an envelope around the capillaries. Previous structural and ultrastructural studies reported various changes in endothelial cells that could affect the function of the BBB. Alteration of the BM may occur in various neurodegenerative diseases.[1] ageing BM becomes thicker and stiffer as the proportion of collagens and laminins changes.[14] A recent study reported microvascular fibrosis, and amorphous fibrosis in the BM of the BBB in ageing.[8] BM ultrastructural changes included focal thickening, splitting and duplication, as well as accumulation of amorphous material of unknown composition and of membranous inclusions identified as degenerated pericytes.[8]. This study focused on the ultrastructural changes of the BBB in ageing but otherwise healthy C57Bl/6J mice and revealed an unexpected accumulation of lipids in the BM of brain capillaries which, to our knowledge, was not previously reported
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