ABSTRACT
The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1-expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 (Mfn2) gene in Dmp1-expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.
Subject(s)
Astrocytes , Blood-Brain Barrier , Endothelial Cells , Mitochondria , Astrocytes/metabolism , Blood-Brain Barrier/metabolism , Animals , Mitochondria/metabolism , Mice , Endothelial Cells/metabolism , GTP Phosphohydrolases/metabolism , GTP Phosphohydrolases/geneticsABSTRACT
Transcortical vessels (TCVs) provide effective communication between bone marrow vascular system and external circulation. Although osteocytes are in close contact with them, it is not clear whether osteocytes regulate the homeostasis of TCVs. Here, we show that osteocytes maintain the normal network of TCVs by transferring mitochondria to the endothelial cells of TCV. Partial ablation of osteocytes causes TCV regression. Inhibition of mitochondrial transfer by conditional knockout of Rhot1 in osteocytes also leads to regression of the TCV network. By contrast, acquisition of osteocyte mitochondria by endothelial cells efficiently restores endothelial dysfunction. Administration of osteocyte mitochondria resultes in acceleration of the angiogenesis and healing of the cortical bone defect. Our results provide new insights into osteocyte-TCV interactions and inspire the potential application of mitochondrial therapy for bone-related diseases.
Subject(s)
Angiogenesis , Osteocytes , Osteocytes/metabolism , Endothelial Cells , Bone and Bones , MitochondriaABSTRACT
The development of nanoporous organic polymers with cycloaliphatic components for effective benzene (Bz) and cyclohexane (Cy) adsorption/separation poses a significant challenge. This work focuses on synthesizing NOP-Ad-1, a nanoporous organic polymer derived from a Friedel-Crafts reaction between cycloaliphatic 1,3-dibromadantane and aromatic hexaphenylbenzene. At 298 K and P/P0 = 0.95, NOP-Ad-1 can uptake 989 mg g-1 benzene and 441 mg g-1 cyclohexane. Moreover, as the benzene vapor ratio increased from 20% to 80%, the Bz/Cy selectivity of NOP-Ad-1 gradually decreased from 1.75 to 1.24. These findings highlight the potential application of NOP-Ad-1 in the adsorption/separation of Bz/Cy mixtures.
