{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:18:54Z","timestamp":1779916734909,"version":"3.53.1"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Government","award":["2020R1F1A1072018"],"award-info":[{"award-number":["2020R1F1A1072018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>In this study, the effects of a 12-week exercise program combining aerobic and resistance training on high-fat diet-induced obese Sprague Dawley (SD) rats after the injection of beta-amyloid into the cerebral ventricle were investigated. Changes in physical fitness, cognitive function, blood levels of beta-amyloid and metabolic factors, and protein expressions of neurotrophic factors related to brain function such as BDNF (brain-derived neurotrophic factor) in the quadriceps femoris, hippocampus, and cerebral cortex were analyzed. The subjects were thirty-two 10-week-old SD rats (DBL Co., Ltd., Seoul, Korea). The rats were randomized into four groups: \u03b2-Non-Ex group (n = 8) with induced obesity and \u03b2A25-35 injection into the cerebral ventricle through stereotactic biopsy; \u03b2-Ex group (n = 8) with induced obesity, \u03b2A25-35 injection, and exercise; S-Non-Ex group (n = 8) with an injection of saline in lieu of \u03b2A25-35 as the control; and S-Ex group (n = 8) with saline injection and exercise. The 12-week exercise program combined aerobic training and resistance training. As for protein expressions of the factors related to brain function, the combined exercise program was shown to have a clear effect on activating the following factors: PGC-1\u03b1 (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), FNDC5 (fibronectin type III domain-containing protein 5), and BDNF in the quadriceps femoris; TrkB (Tropomyosin receptor kinase B), FNDC5, and BDNF in the hippocampus; PGC-1\u03b1, FNDC5, and BDNF in the cerebral cortex. The protein expression of \u03b2-amyloid in the cerebral cortex was significantly lower in the \u03b2-Ex group than in the \u03b2-Non-Ex group (p &lt; 0.05). The 12-week intervention with the combined exercise program of aerobic and resistance training was shown to improve cardiopulmonary function, muscular endurance, and short-term memory. The results demonstrate a set of positive effects of the combined exercise program, which were presumed to have arisen mainly due to its alleviating effect on \u03b2-amyloid plaques, the main cause of reduced brain function, as well as the promotion of protein expressions of PGC-1\u03b1, FNDC5, and BDNF in the quadriceps femoris, hippocampus, and cerebral cortex.<\/jats:p>","DOI":"10.3390\/ijerph19137921","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T23:59:22Z","timestamp":1656460762000},"page":"7921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of an Exercise Program Combining Aerobic and Resistance Training on Protein Expressions of Neurotrophic Factors in Obese Rats Injected with Beta-Amyloid"],"prefix":"10.3390","volume":"19","author":[{"given":"Gyuho","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Physical Education, College of Physical Education, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunwook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physical Education, College of Physical Education, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hee","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoo","family":"Yoon","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayoung","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Physical Education, College of Physical Education, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3724-7758","authenticated-orcid":false,"given":"Kijin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physical Education, College of Physical Education, Keimyung University, Daegu 42601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.2174\/1871527315666151111121749","article-title":"Aging process, cognitive decline and alzheimer\u2019s disease: Can strength training modulate these responses?","volume":"14","author":"Eduardo","year":"2015","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nrneurol.2014.44","article-title":"Alzheimer disease: Lessons from immunotherapy for Alzheimer disease","volume":"10","author":"Wang","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","first-page":"8","article-title":"Dietary topoisomerase II\u2013poisons: Contribution of soy products to infant leukemia?","volume":"1","author":"Hengstler","year":"2002","journal-title":"EXCLI J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"bvaa120","DOI":"10.1210\/jendso\/bvaa120","article-title":"Androgen therapy in neurodegenerative diseases","volume":"4","author":"Bianchi","year":"2020","journal-title":"J. Endocr. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1210\/endrev\/bnz005","article-title":"The role of sex and sex hormones in neurodegenerative diseases","volume":"41","author":"Vegeto","year":"2020","journal-title":"Endocr Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bbr.2017.03.044","article-title":"Protective effects of different exercise modalities in an Alzheimer\u2019s disease-like model","volume":"328","author":"Ozbeyli","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"645","DOI":"10.2174\/1567205014666161213121353","article-title":"Exercise prevents cognitive function decline and demyelination in the white matter of APP\/PS1 transgenic AD mice","volume":"14","author":"Zhang","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_8","first-page":"1045","article-title":"Aerobic exercise improves quality of life, psychological well-being and systemic inflammation in subjects with Alzheimer\u2019s disease","volume":"16","author":"Shehab","year":"2016","journal-title":"Afr. Health Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2340\/16501977-1931","article-title":"Interval training-induced alleviation of rigidity and hypertonia in patients with Parkinson\u2019s disease is accompanied by increased basal serum brain-derived neurotrophic factor","volume":"47","author":"Jaroslaw","year":"2015","journal-title":"J. Rehabil. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC-1\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Bostrom","year":"2012","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5115\/acb.2016.49.1.1","article-title":"The association between PGC-1\u03b1 and Alzheimer\u2019s disease","volume":"49","author":"Sweeney","year":"2016","journal-title":"Anat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1242\/jeb.048397","article-title":"The biological control of voluntary exercise, spontaneous physical and daily energy expenditure in relation to obesity: Human and rodent perspectives","volume":"214","author":"Garland","year":"2011","journal-title":"J. Exp. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainresbull.2016.03.012","article-title":"Physical activity and exercise attenuate neuroinflammation in neurological diseases","volume":"125","author":"Lindsay","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.actpsy.2014.06.011","article-title":"A single bout of resistance exercise can enhance episodic memory performance","volume":"153","author":"Weinberg","year":"2014","journal-title":"Acta Psychol."},{"key":"ref_15","first-page":"505","article-title":"Frailty and sarcopenia: A new bridge to dementia","volume":"74","author":"Naoki","year":"2016","journal-title":"Jpn. J. Clin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jshs.2020.01.004","article-title":"Physical exercise in the prevention and treatment of Alzheimer\u2019s disease","volume":"9","author":"Millan","year":"2020","journal-title":"J. Sport Health Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/bjsports-2016-096587","article-title":"Exercise interventions for cognitive function in adults older than 50: A systematic review with meta-analysis","volume":"52","author":"Northey","year":"2018","journal-title":"Br. J. Sports Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"830824","DOI":"10.3389\/fnagi.2022.830824","article-title":"Effectiveness of physical activity interventions on cognition, neuropsychiatric symptoms, and quality of life of Alzheimer\u2019s disease: An update of a systematic review and meta-analysis","volume":"14","author":"Liang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_19","first-page":"55","article-title":"Effects of resistance exercise and fermented soybean ingestion on the appearance of inflammatory cytokine, metabolic risk factors, and the body composition in obesity-induced white rats","volume":"5","author":"Lee","year":"2020","journal-title":"Int. J. Crisis Saf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"666","DOI":"10.11002\/kjfp.2017.24.5.666","article-title":"Effects of long-term endurance exercise and Salvia miltiorrhiza vinegar on body composition and insulin resistance in high fat diet-induced obese rats","volume":"24","author":"Kim","year":"2017","journal-title":"Korean J. Food Preserv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ejphar.2013.11.034","article-title":"Repeated intra-hippocampal injection of beta-amyloid 25\u201335 induces a reproducible impairment of learning and memory: Considering caspase-3 and MAPKs activity","volume":"726","author":"Ghasemi","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1006\/nlme.1996.3747","article-title":"Insular cortex and amygdala lesions induced after aversive training impair retention: Effects of degree of training","volume":"67","author":"Bermudez","year":"1997","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","article-title":"Developments of a water-maze procedure for studying spatial learning in the rat","volume":"11","author":"Morris","year":"1984","journal-title":"J. Neurosci. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.nlm.2011.09.008","article-title":"Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat","volume":"97","author":"Cechetti","year":"2012","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ahn, N., and Kim, K. (2020). Effects of aerobic and resistance exercise on myokines in high fat diet-induced middle-aged obese rats. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17082685"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1249\/MSS.0000000000002294","article-title":"Effects of exercise training on anxious\u2013depressive-like behavior in Alzheimer rat","volume":"52","author":"Wu","year":"2020","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1249\/MSS.0000000000001519","article-title":"Beneficial effects of exercise pretreatment in a sporadic Alzheimer\u2019s rat model","volume":"50","author":"Wu","year":"2018","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mcn.2017.11.008","article-title":"Exercise decreases BACE and APP levels in the hippocampus of a rat model of Alzheimer\u2019s disease","volume":"86","author":"Alkadhi","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2190\/PM.41.1.c","article-title":"Exercise for the treatment of depression and anxiety","volume":"41","author":"Carek","year":"2011","journal-title":"Int. J. Psychiatry Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mee-inta, O., Zhao, Z., and Kuo, Y. (2019). Physical exercise inhibits inflammation and microglial activation. Cells, 8.","DOI":"10.3390\/cells8070691"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1alpha\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1152\/japplphysiol.00566.2004","article-title":"Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors","volume":"98","author":"Fairey","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.3389\/fimmu.2018.02187","article-title":"Effects of acute and chronic exercise on immunological parameters in the elderly aged: Can physical activity counteract the effects of aging?","volume":"9","author":"Sellami","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nn.4017","article-title":"The case for rejecting the amyloid cascade hypothesis","volume":"18","author":"Herrup","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eaan8821","DOI":"10.1126\/science.aan8821","article-title":"Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer\u2019s mouse model","volume":"361","author":"Choi","year":"2018","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.bbrc.2018.12.148","article-title":"Mitochondrial calcium dysfunction contributes to autophagic cell death induced by MPP+via AMPK pathway","volume":"509","author":"Zhao","year":"2019","journal-title":"Biochem. Biophys. Commun."},{"key":"ref_37","first-page":"507","article-title":"Treadmill exercise prevents learning and memory impairment in Alzheimer\u2019s disease-like pathology","volume":"10","author":"Dao","year":"2013","journal-title":"J. Med. Food"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18793","DOI":"10.1074\/jbc.M611252200","article-title":"Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation","volume":"282","author":"Wright","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2017.05.024","article-title":"Swimming exercise prevents behavioural disturbances induced by an intracerebroventricular injection of amyloid-\u03b21-42 peptide through modulation of cytokine\/NF-kappaB pathway and indolemine-2,3-dioxygenase in mouse brain","volume":"331","author":"Souza","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1139\/apnm-2018-0545","article-title":"The effect of preventive exercise on the neuroprotection in 6-hydroxydopamine-lesioned rat brain","volume":"44","author":"Rezaee","year":"2019","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/jnc.14034","article-title":"Exercise and BDNF reduce A\u03b2 production by enhancing \u03b1-secretase processing of APP","volume":"142","author":"Saket","year":"2017","journal-title":"J. Neurochem."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/13\/7921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:43Z","timestamp":1760139583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/13\/7921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,28]]},"references-count":41,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijerph19137921"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19137921","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,28]]}}}