Exogenous TGF-β1 in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice 2021

[pattismith]

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

by



Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea
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Published: 4 March 2021
(This article belongs to the Section Molecular Biology)
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Abstract

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.

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[Pyrrhus]

This is a very interesting find @pattismith, thanks for sharing it!

Perhaps I find it interesting for its cultural significance.

ME/cfs is rarely mentioned in Korea, so I find it interesting that they used current terminology (ME/cfs) in the abstract, albeit not in the title.

(Which doesn't mean that this mouse model of cytokine-driven central fatigue is necessarily relevant, but it is indeed very interesting...)

 

[andyguitar]

The reduction in Tyrosine Hydroxylase caught my eye @pattismith

 

[pattismith]

@Pyrrhus , yes it's interesting that they tag ME/CFS for their article, maybe long covid produce some gain in interest for our illness?

The reduction in Tyrosine Hydroxylase caught my eye @pattismith

I think the mesolimbic dopaminergic system is a key in both generation of neuropathic central pain and neuropathic central fatigue.

This pathway starts in the ventral tegmental area ..... so this article caught my eye, but it doesn't mean that TGF-beta1 is really implicated in vivo in human neuropathic central fatigue.

 

[bread.]

@Janet Dafoe abilify?

 

[pattismith]

some studies suggesting positive effect of TGF-β1 down-regulation in hypothalamus or striatum in mice

TGF-β1 down-regulation in the mediobasal hypothalamus attenuates hypothalamic inflammation and protects against diet-induced obesity - ScienceDirect

Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1 - ScienceDirect

Sitagliptin and liraglutide reversed nigrostriatal degeneration of rodent brain in rotenone-induced Parkinson’s disease | SpringerLink

 

[S-VV]

I too:
have neuropathic and central pain (gets worse on exertion)
hate TGF-beta after researching it
have great symptom relief by dopaminergic substances

I also have pain in the lymph nodes, especially in the cervical chain and axillary region. I was wondering, @pattismith, if you have similar lymphatic pain

 

[JoeS]

Dopamine plays a number of roles in several brain functions, including important roles in behavior and cognition, sleep, mood, attention, memory and learning.

That's why I felt totally cured for a week when I used cannabis. THC increases dopamine. But I overdid cannabis and got anxiety. After quitting I got post acute withdrawal syndrome on top of ME/CFS symptoms and felt like zombie for 3 months - no energy at all, max brainfog and depression, etc.

 

[pattismith]

I too:
have neuropathic and central pain (gets worse on exertion)
hate TGF-beta after researching it
have great symptom relief by dopaminergic substances

I also have pain in the lymph nodes, especially in the cervical chain and axillary region. I was wondering, @pattismith, if you have similar lymphatic pain

Do you mean that high TGF-beta showed up in your blood test?

I know many ME/CFS patients have lymph nodes pain, but I never had this problem in 35 years.