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Microglia regulate basal cerebral blood flow and neurovascular coupling through ectonucleotidase CD39

ABSTRACT: Microglia tightly interact with brain capillaries and regulate blood brain barrel permeability in pathological conditions. However, it is still unknown whether and how microglia regulate CBF in homeostatic condition. Here we show microglia directly regulate cerebral blood flow (CBF) and neurovascular coupling. Conditional knockout of microglial CD39 resulted in CBF hyper perfusion, reduced ATP induced CBF increase, impaired neurovascular coupling by whisker stimulation and reduced whisker stimulation induced adenosine increase in barrel cortex. Out data suggest that microglia is an important player for CBF regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE223314 | GEO | 2023/07/01

REPOSITORIES: GEO

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Microglia regulate basal cerebral blood flow and neurovascular coupling through ectonucleotidase CD39 II

Project description:Microglia modulate cerebral blood flow and cerebrovascular reactivity, but the mechanisms remain elusive. Here we show that pharmacological or genetic method induced microglia-ablation, which causes reduction of the microglia-expressed ATP/ADP-hydrolyzing ectonucleotidase CD39, elevates the cerebral blood flow baseline, while reducing the cerebral blood flow change to whisker stimulation and intra-cisterna magna injection of ATP, but not adenosine. Microglia P2ry12 inhibition with clopidogrel increased basal cerebral blood flow and the effect was abolished in microglia specific CD39 knockout mice. P2ry12 knockout mice show reduced cerebral blood flow changes to whisker stimulation or intra-cisterna magna injection of ATP. Microglia-specific deletion of CD39 or its pharmacological inhibition reproduces the effects of microglia ablation on cerebral blood flow and attenuates whisker stimulation-induced adenosine concentration increase in contralateral barrel cortex. These results suggest that microglia-dependent adenosine production is an integral component of the brain purinergic signaling system that governs neurovascular coupling.

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Project description:This data set is for the article: Endothelial-neuronal coupling revealed in a decoupled neurovascular unit based Organ-on-Chip approach.

2017-08-24 | MSV000081480 | MassIVE

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