Neurons regulate vascular integrity in the brain by releasing exosomes containing miR-132

On April 21, the journal Cell Research published a research paper entitled "Neurons regulate the vascular integrity of the brain by releasing exosomes containing miR-132" from the Institute of Neuroscience of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences, the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences, and the DuJulin Research Group of the National Key Laboratory of Neuroscience.
the study found that neurons regulate cerebrovascular integrity by releasing exosomes to transport highly expressed miR-132 neurons into cerebrovascular endotrote cells, and then by targeting eef2k to maintain high expression of VE-cadherin.
the work revealed new mechanisms for neurons to regulate cerebrovascular development, and for the first time discovered this neuro-vascular regulation mediated by exosomes.
endoblast cells that make up the capillaries of the brain form a blood-brain barrier by forming close connections and interacting with surrounding weekly and astrogenic glial cells.
blood-brain barrier finely controls the exchange of blood and brain tissue to maintain the stability of the micro-environment in the brain.
damage to cerebrovascular integrity can lead to or exacerbate a range of neurological diseases.
in the field of cerebrovascular development, previous studies have found that cerebrovascular development has many specificity relative to peripheral blood vessels, but it is not clear how the nervous system regulates cerebrovascular development and the formation of blood-brain barriers.
to study how the nervous system regulates cerebrovascular development, the researchers used zebrafish as a model to first examine the role of highly expressive miR-132 in cerebrovascular development.
found that the downward or mutation miR-132 damaged the cerebrovascular integrity of zebrafish and was accompanied by severe in-brain bleeding.
To detect cellular and molecular mechanisms that damage cerebrovascular integrity, the researchers tested the connection proteins, cytostoin transport, and peritonal cell coverage between endoblast cells that are critical to maintaining cerebrovascular integrity, and found that vein endoblast cell connection proteins (VE-cadherin) and its in-cytokine beta-catenin were involved in the destruction of cerebrovascular integrity, while cell transport and peritonal cells were not involved.
the neuron miR-132 was specific to reduce the neuron miR-132 and found that the neuron miR-132 was necessary to maintain cerebrovascular integrity.
(A) 3-day-old cofocus image of zebrafish larvae cerebrovascular network, where eGFP (green) marks vascular endothelial cells and tdTomato (red) marks neurons.
(B) mechanism model: neurons release exosomes containing miR-132 and are devoured by cerebrovascular enditeral cells.
miR-132 in vascular endothor cells by targeting and inhibiting the expression of eef2k, which in turn increases the expression of Cdh5, ultimately promoting the development of cerebrovascular integrity.
Importantly, studies have found that raising or lowering levels of miR-132 in neurons can lead to a corresponding change in miR-132 levels in the endotrine of blood vessels, while specifically lowering levels of miR-132 in endotrin cells also leads to a decrease in VE-cadherin expression and damage to cerebrovascular integrity.
further, the researchers combined experiments with zebrafish living and estopathic culture mammalian cells to find that neurons release exosomes containing miR-132 into vascular endothor cells, which in turn regulate the level of vascular endothort cells miR-132.
the secretion of exosomes can lead to a decrease in the level of miR-132 in endotrotor cells and damage to cerebrovascular integrity.
, the microarray test found that eukaryotic elongation factor 2 kinase (eef2k) is a direct downstream target gene of miR-132, and mediates the expression of miR-132 to VE-cadherin and the regulation of cerebrovascular integrity.
this work found new functions of miR-132 in cerebrovascular development, and revealed exosomes as a new carrier of neuromodulation of cerebrovascular integrity.
the findings provide a new direction for the study of neurovascular interactions mediated by neuron exosomes.
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