Editors' ChoiceNeuroscience

More inflammatory with age

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Science Signaling  09 Jul 2019:
Vol. 12, Issue 589, eaay6126
DOI: 10.1126/scisignal.aay6126

VCAM1-dependent inflammation in aged brain endothelial cells suppresses neurogenesis and cognitive performance.

Aging results in neuroinflammation induced by the activation of microglia, the resident immune cells in the brain. Aging also attenuates neurogenesis due to a decrease in the numbers and activity of stem cells in the dentate gyrus in the hippocampus. Yousef et al. investigated how aging triggers neuroinflammation and suppresses neurogenesis and hippocampal-dependent learning and memory. Brain endothelial cells (BECs) are an important component in the blood-brain barrier. In aged mice or mice injected retro-orbitally with proinflammatory cytokines, BECs showed increased mRNA and protein abundance for VCAM1, a cell adhesion protein that mediates inflammatory responses in endothelial cells. The infusion of plasma from aged mice into young mice increased VCAM1 abundance on BECs and in blood vessels, reduced the proliferation and/or numbers of neural progenitor cells and immature neurons in the dentate gyrus, and stimulated microglial activation. These effects were reversed by the deletion of Vcam1 in BECs or injection of a monoclonal antibody directed against VCAM1. In addition, the VCAM1 antibody improved hippocampal-dependent learning and memory in aged mice. Thus, aging enhances VCAM1-dependent inflammatory responses in endothelial cells in the brain, resulting in reduced neurogenesis and cognitive performance.

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