Cargando…

Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice

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 pat...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Won Kil, Kim, Yeongyeong, Jang, Heejin, Sim, Joo Hye, Choi, Hye Jin, Shin, Younmin, Choi, Jeong June
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961432/
https://www.ncbi.nlm.nih.gov/pubmed/33806649
http://dx.doi.org/10.3390/ijms22052580
_version_ 1783665259474583552
author Lee, Won Kil
Kim, Yeongyeong
Jang, Heejin
Sim, Joo Hye
Choi, Hye Jin
Shin, Younmin
Choi, Jeong June
author_facet Lee, Won Kil
Kim, Yeongyeong
Jang, Heejin
Sim, Joo Hye
Choi, Hye Jin
Shin, Younmin
Choi, Jeong June
author_sort Lee, Won Kil
collection PubMed
description 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)-β1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-β1 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-β1 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-β1. Intracranial injection of TGF-β1 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-β1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-β1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-β1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.
format Online
Article
Text
id pubmed-7961432
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79614322021-03-17 Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice Lee, Won Kil Kim, Yeongyeong Jang, Heejin Sim, Joo Hye Choi, Hye Jin Shin, Younmin Choi, Jeong June Int J Mol Sci Article 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)-β1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-β1 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-β1 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-β1. Intracranial injection of TGF-β1 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-β1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-β1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-β1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease. MDPI 2021-03-04 /pmc/articles/PMC7961432/ /pubmed/33806649 http://dx.doi.org/10.3390/ijms22052580 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Won Kil
Kim, Yeongyeong
Jang, Heejin
Sim, Joo Hye
Choi, Hye Jin
Shin, Younmin
Choi, Jeong June
Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
title Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
title_full Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
title_fullStr Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
title_full_unstemmed Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
title_short Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
title_sort exogenous transforming growth factor-β in brain-induced symptoms of central fatigue and suppressed dopamine production in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961432/
https://www.ncbi.nlm.nih.gov/pubmed/33806649
http://dx.doi.org/10.3390/ijms22052580
work_keys_str_mv AT leewonkil exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice
AT kimyeongyeong exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice
AT jangheejin exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice
AT simjoohye exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice
AT choihyejin exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice
AT shinyounmin exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice
AT choijeongjune exogenoustransforminggrowthfactorbinbraininducedsymptomsofcentralfatigueandsuppresseddopamineproductioninmice