{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:57:44Z","timestamp":1788411464078,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre Poland","doi-asserted-by":"publisher","award":["UMO-2011\/01\/D\/NZ7\/04405"],"award-info":[{"award-number":["UMO-2011\/01\/D\/NZ7\/04405"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mossakowski Medical Research Institute","award":["UMO-2011\/01\/D\/NZ7\/04405"],"award-info":[{"award-number":["UMO-2011\/01\/D\/NZ7\/04405"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intensive aerobic exercise slows the progression of movement disorders in Parkinson\u2019s disease (PD) and is therefore recommended as an important component of treatment for PD patients. Studies in animal models of PD have shown that vigorous exercise has neuroprotective effects, and emerging evidence suggests that it may be a disease-modifying treatment in humans. However, many people with PD may not be able to participate in vigorous exercise because of multiple medical conditions that severely limit their physical activity. In this study, we have shown that chronic MPTP treatment in sedentary mice resulted in loss of dopaminergic neurons in the SNpc, decreased levels of neurotrophins, BDNF and GDNF, and increased levels of inflammatory markers and pro-inflammatory changes in immunocompetent cells. Moderate exercise, initiated both before and after chronic MPTP treatment, significantly attenuated the loss of dopaminergic neurons and increased BDNF and GDNF levels even above those in sedentary control mice. No signs of inflammation were observed in MPTP-treated mice, either when training began before or after MPTP treatment. Training induced beneficial changes in the dopaminergic system, increased levels of neurotrophins and suppression of inflammation were similar for both steady moderate (present data) and intense training (our previously published data). This suggests that there is a kind of saturation when the percentage of rescued dopaminergic neurons reaches the highest possible value, and therefore further increases in exercise intensity do not enhance neuroprotection. In conclusion, our present results compared with the previous data show that increasing exercise intensity beyond the level used in this study does not increase the neuroprotective effect of aerobic training in a mouse model of Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms26031146","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T10:44:30Z","timestamp":1738061070000},"page":"1146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Steady Moderate Exercise Confers Resilience Against Neurodegeneration and Neuroinflammation in a Mouse Model of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-3762","authenticated-orcid":false,"given":"Ewelina","family":"Palasz","sequence":"first","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gasiorowska-Bien","sequence":"additional","affiliation":[{"name":"Clinical and Research Department of Applied Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Drapich","sequence":"additional","affiliation":[{"name":"Clinical and Research Department of Applied Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktor","family":"Niewiadomski","sequence":"additional","affiliation":[{"name":"Clinical and Research Department of Applied Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3294-743X","authenticated-orcid":false,"given":"Grazyna","family":"Niewiadomska","sequence":"additional","affiliation":[{"name":"Clinical and Research Department of Applied Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"},{"name":"Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Emamzadeh, F.N., and Surguchov, A. (2018). Parkinson\u2019s Disease: Biomarkers, Treatment, and Risk Factors. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00612"},{"key":"ref_2","first-page":"215","article-title":"Exercise and neuroplasticity in persons living with Parkinson\u2019s disease","volume":"45","author":"Hirsch","year":"2009","journal-title":"Eur. J. Phys. Rehabil. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mitchell, A.K., Bliss, R.R., and Church, F.C. (2024). Exercise, Neuroprotective Exerkines, and Parkinson\u2019s Disease: A Narrative Review. Biomolecules, 14.","DOI":"10.3390\/biom14101241"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2007.06.011","article-title":"Exercise builds brain health: Key roles of growth factor cascades and inflammation","volume":"30","author":"Cotman","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mahalakshmi, B., Maurya, N., Lee, S.D., and Bharath Kumar, V. (2020). Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165895"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4103\/aian.AIAN_169_18","article-title":"Role of Physical Activity in Parkinson\u2019s Disease","volume":"21","author":"Bhalsing","year":"2018","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2015.04.004","article-title":"Parkinson\u2019s disease and intensive exercise therapy--a systematic review and meta-analysis of randomized controlled trials","volume":"353","author":"Uhrbrand","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/ane.13579","article-title":"Parkinson\u2019s disease and intensive exercise therapy\u2014An updated systematic review and meta-analysis","volume":"145","author":"Gamborg","year":"2022","journal-title":"Acta Neurol. Scand."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1001\/jamaneurol.2017.3517","article-title":"Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial","volume":"75","author":"Schenkman","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_10","first-page":"S21","article-title":"The Universal Prescription for Parkinson\u2019s Disease: Exercise","volume":"10","author":"Alberts","year":"2020","journal-title":"J. Park. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000007937","article-title":"Muscle weakness in Parkinson\u2019s disease: Isokinetic study of the lower limbs","volume":"39","author":"Kakinuma","year":"1998","journal-title":"Eur. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/mds.23127","article-title":"Lowered cardiac sympathetic nerve performance in response to exercise in Parkinson\u2019s disease","volume":"25","author":"Nakamura","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pechstein, A.E., Gollie, J.M., and Guccione, A.A. (2020). Fatigability and Cardiorespiratory Impairments in Parkinson\u2019s Disease: Potential Non-Motor Barriers to Activity Performance. J. Funct. Morphol. Kinesiol., 5.","DOI":"10.3390\/jfmk5040078"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wei, L., Tan, M., Yang, Z., Gao, B., Li, J., Liu, Y., Zikereya, T., Shi, K., and Chen, W. (2024). Aerobic exercise improves motor dysfunction in Parkinson\u2019s model mice via differential regulation of striatal medium spiny neuron. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-63045-4"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Palasz, E., Niewiadomski, W., Gasiorowska, A., Wysocka, A., Stepniewska, A., and Niewiadomska, G. (2019). Exercise-Induced Neuroprotection and Recovery of Motor Function in Animal Models of Parkinson\u2019s Disease. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.01143"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.pneurobio.2018.11.003","article-title":"Exercise as a therapeutic intervention for motor and non-motor symptoms in Parkinson\u2019s disease: Evidence from rodent models","volume":"172","author":"Crowley","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.brainres.2010.01.053","article-title":"Exercise protects against MPTP-induced neurotoxicity in mice","volume":"1341","author":"Gerecke","year":"2010","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8215017","DOI":"10.1155\/2019\/8215017","article-title":"Neuroplasticity and Neuroprotective Effect of Treadmill Training in the Chronic Mouse Model of Parkinson\u2019s Disease","volume":"2019","author":"Palasz","year":"2019","journal-title":"Neural Plast."},{"key":"ref_19","first-page":"RA17","article-title":"Mechanisms of MPTP toxicity and their implications for therapy of Parkinson\u2019s disease","volume":"11","author":"Watanabe","year":"2005","journal-title":"Med. Sci. Monit."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Blesa, J., Phani, S., Jackson-Lewis, V., and Przedborski, S. (2012). Classic and New Animal Models of Parkinson\u2019s Disease. J. Biomed. Biotechnol., 2012.","DOI":"10.1155\/2012\/845618"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gerfen, C.R. (2023). Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective. Front. Syn. Neurosci., 14.","DOI":"10.3389\/fnsyn.2022.1002960"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/ejn.14102","article-title":"Trophic factors for Parkinson\u2019s disease: Where are we and where do we go from here?","volume":"49","author":"Paul","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_23","first-page":"713","article-title":"The role of trophic factors and inflammatory processes in physical activity-induced neuroprotection in Parkinson\u2019s disease","volume":"71","author":"Niewiadomska","year":"2017","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gerecke, K.M., Jiao, Y., Pagala, V., and Smeyne, R.J. (2012). Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043250"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.nbd.2009.11.004","article-title":"Neuroinflammation in Parkinson\u2019s disease: Its role in neuronal death and implications for therapeutic intervention","volume":"37","author":"Tansey","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3109\/00207454.2014.982795","article-title":"Neuroinflammation in Parkinson\u2019s disease: Role in neurodegeneration and tissue repair","volume":"125","author":"Vivekanantham","year":"2015","journal-title":"Int. J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.neuroscience.2018.03.015","article-title":"Endurance Exercise Mediates Neuroprotection Against MPTP-mediated Parkinson\u2019s Disease via Enhanced Neurogenesis, Antioxidant Capacity, and Autophagy","volume":"379","author":"Jang","year":"2018","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/j.1460-9568.2011.07626.x","article-title":"Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson\u2019s disease with moderate neurodegeneration","volume":"33","author":"Lau","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.brainres.2009.10.075","article-title":"Exercise exerts neuroprotective effects on Parkinson\u2019s disease model of rats","volume":"1310","author":"Tajiri","year":"2010","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.neuroscience.2013.01.060","article-title":"BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson\u2019s disease","volume":"237","author":"Real","year":"2013","journal-title":"Neuroscience"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neuroscience.2013.09.042","article-title":"Neuroprotective effects of swimming training in a mouse model of Parkinson\u2019s disease induced by 6-hydroxydopamine","volume":"256","author":"Goes","year":"2014","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"261809","DOI":"10.1155\/2015\/261809","article-title":"Physical Training Regulates Mitochondrial Parameters and Neuroinflammatory Mechanisms in an Experimental Model of Parkinson\u2019s Disease","volume":"2015","author":"Tuon","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s12031-017-0955-4","article-title":"Treadmill Exercise Prevents Increase of Neuroinflammation Markers Involved in the Dopaminergic Damage of the 6-OHDA Parkinson\u2019s Disease Model","volume":"63","author":"Real","year":"2017","journal-title":"J. Mol. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s11064-022-03713-x","article-title":"Modulation of Inflammatory Mediators and Microglial Activation Through Physical Exercise in Alzheimer\u2019s and Parkinson\u2019s Diseases","volume":"47","author":"Ibrahim","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Strohm, A.O., and Majewska, A.K. (2024). Physical exercise regulates microglia in health and disease. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1420322"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ishaq, S., Shah, I.A., Lee, S.-D., and Wu, B.-T. (2025). Effects of exercise training on nigrostriatal neuroprotection in Parkinson\u2019s disease: A systematic review. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1464168"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.neulet.2008.11.065","article-title":"Effects of endurance exercise on ventral tegmental area neurons in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid-treated mice","volume":"450","author":"Ahmad","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0306-4522(03)00096-4","article-title":"Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson\u2019s disease","volume":"119","author":"Tillerson","year":"2003","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pothakos, K., Kurz, M., and Lau, Y.-S. (2009). Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson\u2019s disease with severe neurodegeneration. BMC Neurosci., 10.","DOI":"10.1186\/1471-2202-10-6"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1523\/JNEUROSCI.1069-07.2007","article-title":"Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-lesioned mouse model of basal ganglia injury","volume":"27","author":"Petzinger","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1126\/science.275.5301.838","article-title":"Dopaminergic Neurons Protected from Degeneration by GDNF Gene Therapy","volume":"275","author":"Lin","year":"1997","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0006-8993(99)02191-5","article-title":"Glial cell line derived neurotrophic factor promotes the recovery of dopamine neurons damaged by 6-hydroxydopamine in vitro","volume":"851","author":"Kramer","year":"1999","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbi.2010.09.006","article-title":"Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway","volume":"25","author":"Wu","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.expneurol.2004.11.030","article-title":"Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons","volume":"192","author":"Porritt","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.expneurol.2006.06.006","article-title":"A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra","volume":"202","author":"Boger","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nan.12011","article-title":"Review: Activation patterns of microglia and their identification in the human brain","volume":"39","author":"Boche","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/s41583-018-0057-5","article-title":"Microglial signatures and their role in health and disease","volume":"19","author":"Butovsky","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5607\/en.2013.22.2.59","article-title":"Brain inflammation and microglia: Facts and misconceptions","volume":"22","author":"Jeong","year":"2013","journal-title":"Exp. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.nbd.2014.10.017","article-title":"Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson\u2019s disease","volume":"73","author":"Bortolanza","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.freeradbiomed.2008.05.026","article-title":"Reactive oxygen species up-regulate CD11b in microglia via nitric oxide: Implications for neurodegenerative disease","volume":"45","author":"Roy","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jurga, A.M., Paleczna, M., and Kuter, K.Z. (2020). Overview of General and Discriminating Markers of Differential microglia Phenotypes. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00198"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1046\/j.1471-4159.2003.02213.x","article-title":"Microglia\/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity","volume":"88","author":"Ohsawa","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0014-5793(02)02430-4","article-title":"The allograft inflammatory factor-1 family of proteins","volume":"514","author":"Deininger","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.neuroscience.2017.05.016","article-title":"Treadmill exercise produces neuroprotective effects in a murine model of Parkinson\u2019s disease by regulating the TLR2\/MyD88\/NF-\u03baB signaling pathway","volume":"356","author":"Koo","year":"2017","journal-title":"Neuroscience"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.neuroscience.2015.04.069","article-title":"Intervention with Exercise Restores Motor Deficits But Not Nigrostriatal Loss in a Progressive MPTP Mouse Model of Parkinson\u2019s Disease","volume":"299","author":"Sconce","year":"2015","journal-title":"Neuroscience"},{"key":"ref_56","first-page":"130","article-title":"Exercise, inflammation and aging","volume":"3","author":"Woods","year":"2012","journal-title":"Aging Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1096\/fj.01-0876rev","article-title":"Muscle-derived interleukin-6: Mechanisms for activation and possible biological roles","volume":"16","author":"Febbraio","year":"2002","journal-title":"FASEB J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0047-6374(03)00027-7","article-title":"Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes","volume":"124","author":"Pedersen","year":"2003","journal-title":"Mech. Ageing Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1096\/fj.02-0670fje","article-title":"Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans","volume":"17","author":"Starkie","year":"2003","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1113\/jphysiol.2008.155382","article-title":"Repeated bouts of aerobic exercise lead to reductions in skeletal muscle free radical generation and nuclear factor kappa B activation","volume":"586","author":"Brooks","year":"2008","journal-title":"J. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.tem.2008.12.002","article-title":"ROS and myokines promote muscle adaptation to exercise","volume":"20","author":"Scheele","year":"2009","journal-title":"Trends Endocrinol. Metabol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1249\/MSS.0b013e3181e3ac80","article-title":"Long-term physical activity and inflammatory biomarkers in older adults","volume":"42","author":"Beavers","year":"2010","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-981-13-9913-8_13","article-title":"Microglia in Parkinson\u2019s Disease","volume":"1175","author":"Ho","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/mds.21751","article-title":"Glial reactions in Parkinson\u2019s disease","volume":"23","author":"McGeer","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.nbd.2016.07.009","article-title":"Unconventional neurotrophic factors CDNF and MANF: Structure, physiological functions and therapeutic potential","volume":"97","author":"Lindahl","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2009.03.063","article-title":"Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells","volume":"1274","author":"Tanabe","year":"2009","journal-title":"Brain Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.bbadis.2014.03.003","article-title":"H2O2- or L-DOPA-injured dopaminergic neurons trigger the release of soluble mediators that up-regulate striatal GDNF through different signalling pathways","volume":"1842","author":"Fonseca","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S147","DOI":"10.1016\/S1353-8020(11)70046-3","article-title":"Neurorestoration by physical exercise: Moving forward","volume":"18","author":"Zigmond","year":"2012","journal-title":"Park. Relat. Disord."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41531-024-00641-1","article-title":"Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson\u2019s disease","volume":"10","author":"Hoye","year":"2024","journal-title":"NPJ Park. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/mds.29148","article-title":"Longitudinal Positron Emission Tomography Imaging of Presynaptic Terminals in Early Parkinson\u2019s Disease","volume":"37","author":"Delva","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0014-5793(01)03269-0","article-title":"The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson\u2019s disease","volume":"510","author":"Zecca","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mds.21690","article-title":"Parkinson\u2019s disease and resistive exercise: Rationale, review, and recommendations","volume":"23","author":"Falvo","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/cphy.c100047","article-title":"Parkinson disease and exercise","volume":"3","author":"Earhart","year":"2013","journal-title":"Comp. Physiol."},{"key":"ref_75","first-page":"289","article-title":"Exaggerated pressor response to static squats in Parkinson\u2019s disease (PD) and healthy subjects is likely an individual trait, not influenced by whole body vibration (WBV)","volume":"52","author":"Niewiadomski","year":"2023","journal-title":"NeuroRehabilitation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.advms.2016.11.010","article-title":"Impact of exaggerated blood pressure response in normotensive individuals on future hypertension and prognosis: Systematic review according to PRISMA guideline","volume":"62","author":"Keller","year":"2017","journal-title":"Adv. Med. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/j.1600-0838.2010.01288.x","article-title":"Effect of exercise training intensity on murine T-regulatory cells and vaccination response","volume":"22","author":"Wang","year":"2012","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1089\/rej.2009.0854","article-title":"Neuroprotective effect of long-term NDI1 gene expression in a chronic mouse model of Parkinson disorder","volume":"12","author":"Seo","year":"2009","journal-title":"Rejuven. Res."},{"key":"ref_79","unstructured":"Paxinos, G., and Franklin, K.B.J. (2001). The Mouse Brain in Stereotaxic Coordinates, Academic Press. [2nd ed.]."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.neuroscience.2009.04.031","article-title":"A comparison of model-based (2D) and design-based (3D) stereological methods for estimating cell number in the substantia nigra pars compacta (SNpc) of the C57BL\/6J mouse","volume":"161","author":"Baquet","year":"2009","journal-title":"Neuroscience"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1146\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:55Z","timestamp":1759919875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":80,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031146"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031146","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]}}}