Exercise-Intervened Endothelial Progenitor Cell Exosomes Protect N2a Cells by Improving Mitochondrial Function.

We have recently demonstrated that exosomal communication between endothelial progenitor cells (EPCs) and brain endothelial cells is compromised in hypertensive conditions, which might contribute to the poor outcomes of stroke subjects with hypertension. The present study investigated whether exercise intervention can regulate EPC-exosome (EPC-EX) functions in hypertensive conditions. Bone marrow EPCs from sedentary and exercised hypertensive transgenic mice were used for generating EPC-EXs, denoted as R-EPC-EXs and R-EPC-EXET. The exosomal microRNA profile was analyzed, and EX functions were determined in a co-culture system with N2a cells challenged by angiotensin II (Ang II) plus hypoxia. EX-uptake efficiency, cellular survival ability, reactive oxygen species (ROS) production, mitochondrial membrane potential, and the expressions of cytochrome c and superoxide-generating enzyme (Nox4) were assessed. We found that (1) exercise intervention improves the uptake efficiency of EPC-EXs by N2a cells. (2) exercise intervention restores miR-27a levels in R-EPC-EXs. (3) R-EPC-EXET improved the survival ability and reduced ROS overproduction in N2a cells challenged with Ang II and hypoxia. (4) R-EPC-EXET improved the mitochondrial membrane potential and decreased cytochrome c and Nox4 levels in Ang II plus hypoxia-injured N2a cells. All these effects were significantly reduced by miR-27a inhibitor. Together, these data have demonstrated that exercise-intervened EPC-EXs improved the mitochondrial function of N2a cells in hypertensive conditions, which might be ascribed to their carried miR-27a.

Extracellular Vesicles in Neurodegenerative Diseases: An Update.

Neurodegenerative diseases affect millions of people worldwide. The likelihood of developing a neurodegenerative disease rises dramatically as life expectancy increases. Although it has drawn significant attention, there is still a lack of proper effective treatments for neurodegenerative disease because the mechanisms of its development and progression are largely unknown. Extracellular vesicles (EVs) are small bi-lipid layer-enclosed nanosized particles in tissues and biological fluids. EVs are emerging as novel intercellular messengers and regulate a series of biological responses. Increasing evidence suggests that EVs are involved in the pathogenesis of neurodegenerative disorders. In this review, we summarize the recent findings of EVs in neurodegenerative diseases and bring up the limitations in the field.