Biology subjects

Boppart, M. D.

Publications and source records attributed to Boppart, M. D..

3 recordsLinked to original sources

bioRxiv2025

Exercise-induced plasma-derived extracellular vesicles increase adult hippocampal neurogenesis

Aerobic exercise enhances cognition in part by increasing adult hippocampal neurogenesis, angiogenesis, and astrogliogenesis. Since hippocampal atrophy is a hallmark of several neurological and psychiatric conditions--including depression, PTSD, Alzheimers disease, and aging--understanding the mechanisms by which exercise increases neurogenesis has broad therapeutic relevance. One potential mechanism involves extracellular vesicles (EVs), lipid bilayer-enclosed particles released by multiple tissues during exercise that transport bioactive molecular cargo to distant organs, including the brain. In this study, we tested whether plasma-derived EVs from exercising mice (ExerVs) are sufficient to promote hippocampal neurogenesis, astrogliogenesis, and vascular density in sedentary mice. EVs were isolated from the plasma of sedentary or exercising C57BL/6J mice and injected intraperitoneally into sedentary recipients twice weekly for four weeks. To evaluate reproducibility, the study was conducted across two independent cohorts using identical procedures. ExerV-treated mice showed a significant increase in BrdU-positive cells in the granule cell layer compared to both PBS- and SedV-treated controls in both cohorts. Approximately 90% of these cells co-expressed NeuN, indicating neuronal differentiation, while 6% co-expressed S100{beta}, indicating astrocyte generation. No changes were observed in vascular density across groups. These findings provide initial evidence that systemically delivered exercise-derived EVs can enhance hippocampal neurogenesis and astrogliogenesis in sedentary mice. This proof-of-concept work supports further investigation into ExerVs as a potential therapeutic strategy for conditions associated with hippocampal atrophy. HighlightsO_LIExerVs increase hippocampal neurogenesis and astrogliogenesis in sedentary mice C_LIO_LIExerVs do not affect hippocampal vascular area C_LIO_LICirculating ExerVs are sufficient to recapitulate key brain benefits of exercise C_LI

neuroscience↗

bioRxiv2024

Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells.

Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME). Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast cancer cells, resulting in loss of adherence, increased migratory capacity and resistance to cytotoxic chemotherapy. Decreased microRNAs (miRs) within the sEVs resulted in activation of the WNT/{beta}-catenin signaling pathway in recipient cells and suggest that this may be a predominant pathway for stem-like phenotype and EMT. Our findings underscore a novel mechanism by which 27HC-modulated neutrophils contribute to breast cancer pathophysiology through EV-mediated intercellular communication, suggesting potential therapeutic targets in cancer treatment.

cancer biology↗

bioRxiv2024

Cholesterol Metabolite 27-Hydroxycholesterol Enhances the Secretion of Cancer Promoting Extracellular Vesicles by a Mitochondrial ROS-Induced Impairment of Lysosomal Function

Extracellular vesicles (EVs) serve as crucial mediators of cell-to-cell communication in normal physiology as well as in diseased states, and have been largely studied in regard to their role in cancer progression. However, the mechanisms by which their biogenesis and secretion are regulated by metabolic or endocrine factors remain unknown. Here, we delineate a mechanism by which EV secretion is regulated by a cholesterol metabolite, 27-Hydroxycholesterol (27HC), where treatment of myeloid immune cells (RAW 264.7 and J774A.1) with 27HC impairs lysosomal homeostasis, leading to shunting of multivesicular bodies (MVBs) away from lysosomal degradation, towards secretion as EVs. This impairment of lysosomal function is caused by mitochondrial dysfunction and subsequent increase in reactive oxygen species (ROS). Interestingly, cotreatment with a mitochondria-targeted antioxidant rescued the lysosomal impairment and attenuated the 27HC-mediated increase in EV secretion. Overall, our findings establish how a cholesterol metabolite regulates EV secretion and paves the way for the development of strategies to regulate cancer progression by controlling EV secretion.

cell biology↗