Tracking Skeletal Muscle-Derived Fluorescent Extracellular Vesicle Distribution After Exercise in Transgenic Mice
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Authors
Januszkiewicz, Ethan
Date
2025-07-07
Type
thesis
Language
eng
Keyword
Mice , Exercise , Extracellular vesicles
Alternative Title
Abstract
Exercise induces brain health and beneficial effects in many neurological or neuropsychiatric conditions, ranging from depression, anxiety, to Alzheimer’s disease. The beneficial effects of exercise are partially mediated by the actions of active molecules released by muscles (myokines). However, how and if these molecules reach the brain to exert their neuroprotective actions remain unknown. Extracellular vesicles (EVs) are nanoparticles released by all cell types. EVs carry protein, lipids, and nucleic acid content from their cell origin, and play an essential role in cellular communication. We hypothesize that skeletal muscle-derived EVs containing myokines are released into circulation during exercise and are essential to directly or indirectly translate exercise benefits to the brain. Therefore, in this study, we tracked the organ distribution of fluorescent muscle-EVs in sedentary, acute (treadmill exercise), or chronic exercise (running wheel) conditions in a transgenic mouse model (n=4-5 mice/group). For this, we used an innovative completely novel transgenic mouse model that expresses tamoxifen-induced Cre-recombinase under the myogenin promoter (Myog-Cre) crossed with TIGER mice that express Cre-induced hCD9 tagged with green-fluorescent protein (GFP) allowing for the tracking of muscle specific EVs using fluorescence. Importantly, this transgenic model is the first of its kind. Fluorescence was measured at multiple tissues postmortem. We found a mean 20 to 80 times higher fluorescence intensity in different skeletal muscle types from Myog-CreHET and Myog-CreWT controls, irrespective of exercise condition. We also found increased fluorescence in the brains of chronically exercised mice, particularly in the cortex and hypothalamus. Our findings suggest that muscle-EVs may reach the brain following exercise, albeit in low quantities.
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Attribution-NonCommercial-NoDerivatives 4.0 International