The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Exercise-induced plasma-derived extracellular vesicles increase adult hippocampal neurogenesis
Open accessPreprint — published as 10.1016/j.brainres.2025.150003
Abstract
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, Alzheimer’s 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 S100β, 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. Highlights: ExerVs increase hippocampal neurogenesis and astrogliogenesis in sedentary mice ExerVs do not affect hippocampal vascular area Circulating ExerVs are sufficient to recapitulate key brain benefits of exercise
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Tartt, A. N., Mariani, M. B., Hen, R., Mann, J. J., & Boldrini, M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01520-y · Cited by 408
Flagged first, then by citations
Research works printed but not linked: 70
- 10.1073/pnas.1015950108 · DOI · Paper page
- 10.1136/bjsm.2008.052498 · DOI
- 10.1016/S0197-4580(02)00028-3 · DOI
- 10.1038/nature08983 · DOI · Paper page
- 10.1523/JNEUROSCI.2814-14.2014 · DOI
- 10.1007/7854_2012_220 · DOI · Paper page
- 10.1007/s12017-008-8031-4 · DOI
- 10.1111/j.1601-183X.2010.00674.x · DOI
- 10.1038/6368 · DOI · Paper page
- 10.1523/JNEUROSCI.1661-18.2019 · DOI · Paper page
- 10.1016/j.cmet.2016.05.025 · DOI · Paper page
- 10.1523/JNEUROSCI.21-05-01628.2001 · DOI · Paper page
- 10.1016/j.cmet.2013.09.008 · DOI · Paper page
- 10.1016/j.stemcr.2019.02.009 · DOI · Paper page
- 10.1126/science.aaw2622 · DOI · Paper page
- 10.1038/s41586-021-04183-x · DOI · Paper page
- 10.1111/j.1460-9568.2003.03041.x · DOI · Paper page
- 10.1523/JNEUROSCI.21-05-01628.2001 · DOI · Paper page
- 10.1016/j.cmet.2022.01.005 · DOI
- 10.3389/fnut.2021.685517 · DOI
- 10.3389/fnins.2019.00403 · DOI
- 10.1016/0006-8993(95)01291-5 · DOI
- 10.1523/JNEUROSCI.22-02-00486.2002 · DOI
- 10.1093/biosci/biv084 · DOI
- 10.1016/j.pharmthera.2018.02.013 · DOI
- 10.1038/nri855 · DOI
- 10.1371/journal.pone.0125094 · DOI · Paper page
- 10.1016/j.yexcr.2010.04.006 · DOI · Paper page
- 10.3402/jev.v4.28239 · DOI · Paper page
- 10.1021/acsnano.9b04397 · DOI
- 10.1007/s12195-016-0458-3 · DOI · Paper page
- 10.1186/s40478-017-0470-4 · DOI · Paper page
- 10.3390/ijms21124407 · DOI · Paper page
- 10.1073/pnas.1902513116 · DOI
- 10.1016/j.jconrel.2020.09.019 · DOI
- 10.4137/JEN.S39916 · DOI
- 10.1080/20013078.2020.1809064 · DOI · Paper page
- 10.1002/hipo.20543 · DOI · Paper page
- 10.1007/s00429-012-0500-8 · DOI
- 10.1002/1096-9861(20001002)425:4<479::AID-CNE2>3.0.CO;2-3 · DOI · Paper page
- 10.1002/hipo.20545 · DOI · Paper page
- 10.1016/j.mod.2015.06.001 · DOI
- 10.1016/j.neulet.2005.06.009 · DOI
- 10.1634/stemcells.2007-0513 · DOI
- 10.1038/s41598-020-76356-z · DOI
- 10.1016/j.neuroscience.2023.01.028 · DOI
- Fliflet A , Spradlin R , Tan Y , et al. Exercise stimulates the release of glutathione peroxidase 1 (GPX1)-enriched extracellular vesicles in plasma that promote vascularization in muscle. Under review.
- 10.1016/j.ijbiomac.2023.123740 · DOI
- 10.1016/j.cmet.2022.01.005 · DOI
- 10.1186/s13041-017-0322-y · DOI
- 10.30773/pi.2024.0186 · DOI
- 10.1002/stem.3102 · DOI
- 10.3389/fcell.2023.1124907 · DOI
- 10.1113/JP282867 · DOI
- 10.3402/jev.v4.26316 · DOI · Paper page
- 10.1113/JP282867 · DOI
- 10.1002/jev2.12238 · DOI
- 10.1016/j.ejpb.2021.11.012 · DOI
- 10.1523/JNEUROSCI.1731-05.2005 · DOI · Paper page
- 10.1093/cercor/13.8.845 · DOI
- 10.1002/hipo.22020 · DOI
- 10.1002/hipo.23209 · DOI
- 10.1523/JNEUROSCI.20-08-02926.2000 · DOI · Paper page
- 10.1016/j.brainres.2005.11.062 · DOI · Paper page
- 10.1111/j.1460-9568.2004.03720.x · DOI · Paper page
- 10.1523/JNEUROSCI.0709-12.2012 · DOI · Paper page
- 10.1002/hipo.22551 · DOI
- 10.1002/cne.20493 · DOI · Paper page
- 10.1016/S1474-4422(17)30343-5 · DOI
- 10.1016/S0006-3223(02)01359-8 · DOI · Paper page
Metadata
- Authors
- Connolly, M. G., Fliflet, A. M., Ravi, P., Rosu, D. I., Boppart, M. D., & Rhodes, J. S.
- Affiliations
- University of Alberta (CA)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Rhodes, Justin S.
- Venue
- Brain Research
- Publisher
- openRxiv
- Published
- 2025-08-02
- Volume
- 1869
- Pages
- 150003-150003
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W7094948197
- Cited by
- 4
- References
- 1
- Citations by year
- 2026: 4
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Research (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Funders
- NASA (NNX16AO69A)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- extracellular vesicles, plasma-derived vesicles, aerobic exercise, adult hippocampal neurogenesis, voluntary wheel running, systemic drug delivery, hippocampal atrophy, cognitive enhancement, neuronal differentiation, astrocyte differentiation, sedentary mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
