{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:55:57Z","timestamp":1791557757097,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20201435"],"award-info":[{"award-number":["BK20201435"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Persistent microglial inflammation is a detrimental contributor to the progression of Parkinson disease (PD) pathology and related issues such as impaired adult hippocampal neurogenesis (AHN) and cognition. We conducted a 10\u2010week exercise program with MPTP\u2010treated mice to determine whether neuroinflammation can be addressed by aerobic exercise and elucidate its underlying regulatory mechanisms. Ten weeks of exercise significantly reduced PD\u2010related pathology and enhanced AHN and memory. These changes were linked to a reduction in neuronal apoptosis, microglial inflammation, and NLRP3 inflammasome activation. In cultured microglia, fibril \u03b1\u2010synuclein reduced FNDC5\/irisin protein levels and induced NLRP3 inflammasome formation and IL\u20101\u03b2 production, which could be diminished by recombinant irisin treatment. Interestingly, \u201crunner serum\u201d isolated from exercising rodents enhanced FNDC5\/irisin expression and reduced NLRP3 inflammasome components and IL\u20101\u03b2 secretion in \u03b1\u2010synuclein\u2010treated microglia. These effects could be diminished by blocking irisin signaling with cyclo RGDyk or NLRP3 agonist, nigericin sodium salt. Exercise\u2010induced neuroprotective effects were weakened by treatment of MPTP\u2010treated mice with cyclo RGDyk. In contrast, systematic administration of irisin partially replicated the beneficial effects of exercise on PD pathology, AHN, and memory function. As a nonpharmacological strategy, aerobic exercise effectively addresses PD pathology and preserves adult neurogenesis and cognition by mitigating microglial inflammation via mediating irisin\/NLRP3 inflammasome pathways.<\/jats:p>","DOI":"10.1111\/acel.70061","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T08:12:41Z","timestamp":1744013561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Aerobic Exercise Restores Hippocampal Neurogenesis and Cognitive Function by Decreasing Microglia Inflammasome Formation Through Irisin\/\n                    <scp>NLRP3<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-9506","authenticated-orcid":false,"given":"Renqing","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Physical Education, Yangzhou University  Yangzhou 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