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This study was conducted to determine whether chronic moderate treadmill exercise prevents dopaminergic neuron loss and Lewy body\u2010like inclusion burden in a preclinical model of PD. This study also sought to identify plasma exosome bound \u201cexerkines\u201d with potential to induce neuroprotective brain adaptations. Benefits of exercise are thought to be achieved in part through nucleic acids, lipids, and peptides termed exerkines abundant during exercise. These exerkines can induce cell\u2010specific exercise adaptations culminating in neuroprotection. Membrane\u2010free exerkines are subject to degradation in blood and may not effectively cross the blood\u2010brain barrier to induce brain adaptations to exercise, limiting their inter\u2010organ signaling potential. This led us to hypothesize that exerkines, bioactive RNAs in particular, may be selectively packaged into exosomes and released into plasma during exercise. Exosomes are small extracellular vesicles, selectively packaged and released by cells, with likely important differences in composition at rest, during injury and disease, and in response to exercise. Exosomes have been demonstrated to play a major role in inter\u2010organ communication. Chronic exercise was found to provide neuroprotection to dopaminergic neurons in the substantia nigra pars compacta, without affecting Lewy body\u2010like inclusion burden in the nigra or the striatum. Plasma exosomal RNA was isolated from age\u2010matched exercising and sedentary non\u2010PD rats and sequenced. We report 27 unique RNAs upregulated in the exosomes of exercisers, 3 mRNAs with clear neuroprotective potential.<\/jats:p>","DOI":"10.1002\/jnr.70084","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T18:07:57Z","timestamp":1760378877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Moderate Chronic Treadmill Exercise Slows Dopaminergic Neuron Loss in a Rat Model of Parkinson's Disease and Alters\n                    <scp>RNA<\/scp>\n                    Content of Circulating Plasma Exosomes"],"prefix":"10.1002","volume":"103","author":[{"given":"Bruce A.","family":"Citron","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, VA new Jersey Health Care System  East Orange New Jersey USA"},{"name":"Department of Pharmacology Physiology, &amp; Neuroscience, Rutgers New Jersey Medical School  Newark New Jersey 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