{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:29:47Z","timestamp":1781886587244,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myalgic encephalomyelitis (ME)\/chronic fatigue syndrome (CFS) is one of the most refractory diseases in humans and is characterized by severe central fatigue accompanied with various symptoms that affect daily life, such as impaired memory, depression, and somatic pain. However, the etiology and pathophysiological mechanisms of CFS remain unknown. To investigate the pathophysiological role of transforming growth factor (TGF)-\u03b21, we injected a cytokine into the lateral ventricle of a C57BL\/6 mouse. The intracranial injection of TGF-\u03b21 increased the immobility duration in a forced swimming test (FST) and time spent at the closed arm in elevated plus maze (EPM) analysis. The mice injected with TGF-\u03b21 into their brain showed increased sensitivity to pain in a von Frey test, and had a decreased retention time on rotarod and latency time in a bright box in a passive avoidance test. In addition, the serum levels of muscle fatigue biomarkers, lactate dehydrogenase (LDH) and creatine kinase (CK), were significantly increased after administration of TGF-\u03b21. Intracranial injection of TGF-\u03b21 significantly reduced the production of tyrosine hydroxylase (TH) in the ventral tegmental area, accompanied by a decreased level of dopamine in the striatum. The suppression of TH expression by TGF-\u03b21 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-\u03b21 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-\u03b21 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.<\/jats:p>","DOI":"10.3390\/ijms22052580","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:39:07Z","timestamp":1614904747000},"page":"2580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exogenous Transforming Growth Factor-\u03b2 in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Won Kil","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejin","family":"Jang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hye","family":"Sim","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5213-4105","authenticated-orcid":false,"given":"Younmin","family":"Shin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0469-1307","authenticated-orcid":false,"given":"Jeong June","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12967-020-02269-0","article-title":"Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome\/myalgic encephalomyelitis (CFS\/ME)","volume":"18","author":"Lim","year":"2020","journal-title":"J. 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