Nature uncovers age-related changes in the blood-brain barrier.

The blood-brain barrier (BBB) is the barrier between the brain and the circulatory system of the blood, and its permeability is lowIt is widely believed that the integrity of BBB is necessary to maintain brain functionSo, does BBB's transmission of certain external tracers fully represent the level of its barrier and transport functions?July 1, 2020, the Tony Wyss-Coray team at Stanford University School of Medicine published its latest results online in Nature, finding that as we age, BBB's physiological transport function decreases and its intake of plasma protein decreasesBBB is not completely closed, it in addition to playing a barrier role, but also has transport, immunity and other functionsEach time the heart beats, the BBB is affected by the bloodThis process may lead to local transshipment, signal transduction and other occurrencesThe authors fluorescently labeled a variety of endogenous plasma proteins and found that endogenous circulatory proteins can penetrate into healthy brains under physiological conditionsTo explore the mechanism by which BBB transports plasma proteins, the authors sequenced endothelial cells with single-cell RNA and linked the intake levels of each endothelial cell to the gene expression spectrumThe analysis showed that there was a gradient in the ingestion of plasma proteins by the endothelial cells of the venous treeIts transport increases with the reduction of vascular pressure and is the most ingested in the veinSubsequently, the authors combined published data on aging of the brain endothelial cell transcription group, which showed defects in receptor-mediated transport function (RMT)Moreover, as we age, the transport of endothelial cells in the brain gradually changes from ligand-specific RMT to nonspecific vesicle transportThe authors also quantified the age-varying changes of mesh proteins and vesicles with a high-resolution microscope that dyeed microvascular vessels with antibodiesThey found that in younger mice there were more cytomyloases, while in older mice, vesicles were moreThis result confirms that nonspecific cytoswallowation increases with age, while receptor-mediated specific endoscogulation decreasesBy assessing the changes in vascular density, astrocellular coverage, and weekly cell coverage with age, the authors found that normal aging mice had peripheral cell deletion, ectopic calcification, and dysfunction in BBB These changes are accompanied by the co-location of type I collagen and ALPL, a transport negative regulator Based on this, the author used ALPL inhibitors for further study The results showed that after ALPL inhibition, plasma absorption increased in the essential cells of the aging brain, except for ferritin in general, the authors found an age-related change in plasma protein osmotication in BBB and explained its possible mechanism, and demonstrated the role of ALPL in the change of BBB function associated with aging These findings reveal the mechanism of physiological protein transport in healthy brains, the mechanism of age-related blood-brain barrier dysfunction, and help clinical lying in more efficient ways .