Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue Syndrome.

[Murph]

Front Psychiatry. 2018 Nov 16;9:589. doi: 10.3389/fpsyt.2018.00589. eCollection 2018.
Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue Syndrome.
Noda M1, Ifuku M2, Hossain MS2, Katafuchi T2.
Author information
Abstract
Fatigue is commonly reported in a variety of illnesses and has major impact on quality of life. Chronic fatigue syndrome (CFS) is a debilitating syndrome of unknown etiology. The clinical symptoms include problems in neuroendocrine, autonomic, and immune systems. It is becoming clear that the brain is the central regulator of CFS. For example, neuroinflammation, especially induced by activation of microglia and astrocytes, may play a prominent role in the development of CFS, though little is known about molecular mechanisms. Many possible causes of CFS have been proposed.

However, in this mini-review, we summarize evidence for a role for microglia and astrocytes in the onset and the maintenance of immunologically induced CFS. In a model using virus mimicking synthetic double-stranded RNA, infection causes sequential signaling such as increased blood brain barrier (BBB) permeability, microglia/macrophage activation through Toll-like receptor 3 (TLR3) signaling, secretion of IL-1β, upregulation of the serotonin transporter (5-HTT) in astrocytes, reducing extracellular serotonin (5-HT) levels and hence reduced activation of 5-HT1A receptor subtype. Hopefully, drug discovery targeting these pathways may be effective for CFS therapy.

KEYWORDS:
IL-1beta; TLR3; chronic fatigue syndrome; poly I:C; serotonin transporter

PMID:
30505285
PMCID:
PMC6250825
DOI:
10.3389/fpsyt.2018.00589

 

[Research 1st]

Interesting paper, thanks for sharing.

If our BBB is impaired, then our brains run the risk of being slammed by events people without our condition can shrug off.

E.g. We can end up trashed by a virus that others brush off and return to work. Yet we can report huge increase in brainfog, headache, light and noise sensitivity and vertigo and pain for weeks or months or even years.

To me, this is an abnormal neuro inflammatory CNS response to something as innocent as a common cold that an autoimmune process switches on/off.

So are these pathogens, proteins, lymphocytes literally climbing into our brains? Hopefully we'll find out.

I'm sure the inflammation causes the neuro psych symptoms too, like anxiety and panic disorder many of us are plagued by, post onset, that we never had when healthy

 

[pattismith]

I'm sure the inflammation causes the neuro psych symptoms too, like anxiety and panic disorder many of us are plagued by, post onset, that we never had when healthy

more and more papers point neuroinflammation as a cause of so called psychiatric disorders.

This paper makes me think about the cell danger response of Naviaux. @Pyrrhus
ATP-Nlrp3 Inflammasome-Complement Cascade Axis in Sterile Brain Inflammation in Psychiatric Patients and its Impact on Stem Cell Trafficking
.


Abstract

Recent evidence indicates that the occurrence of psychiatric disorders in patients is linked to a local “sterile” inflammation of brain or due to a systemic inflammation process that affects the central nervous system.

This is supported by the observation that in peripheral blood of psychotic patients are detectable several mediators and markers of inflammation as well as clinical data on correlations between systemic chronic inflammatory processes and psychiatric disorders.

This may explain why some reported anti-inflammatory treatment strategies have beneficial effects on ameliorating psychotic events.

In this review we will present a concept that aberrant purinergic signaling and increases in extracellular level of adenosine triphosphate (ATP) in the brain parenchyma may lead to activation of Nlrp3 inflammasome in microglia cells and as a consequence microglia released danger associated molecular pattern (DAMP) proteins activate complement cascade (ComC) in mannan binding lectin (MBL) – dependent manner.

Activation of ATP-Nlrp3 inflammasome-ComC axis may also orchestrate trafficking of stem cells released from bone marrow into peripheral blood observed in psychotic patients.

Based on this, the ATP-Nlrp3 inflammasome-ComC axis may become a target for new therapeutic approaches, which justifies the development and clinical application of efficient anti-inflammatory treatment strategies targeting this axis in psychiatry.

 

[Pyrrhus]

more and more papers point neuroinflammation as a cause of so called psychiatric disorders.

"so-called psychiatric disorders"

I don't even use the term "psychiatric disorder" anymore, just "neurological disorder".

Another phrase I don't use is "sterile inflammation". Just because you're unsuccessful at finding the cause of the inflammation doesn't make it "sterile"!

 

[pattismith]

"so-called psychiatric disorders"

I don't even use the term "psychiatric disorder" anymore, just "neurological disorder".

I believe psychiatry will move to neuropsychiatry, and that they will become real brain neurologist at the end (well I hope so!)
But it's not an easy work to make such a revolution after more than 100 years of psychiatry!

 

[Rufous McKinney]

I believe psychiatry will move to neuropsychiatry, and that they will become real brain neurologist at the end (well I hope so!)
But it's not an easy work to make such a revolution after more than 100 years of psychiatry!

Bizarre- that all this chemistry and messed up physical chemistry- is being published in psych journals.

good: for them to realize its not peoples thoughts- its another Physical Ailment.

Yet it seems like Isn't This Neurology?

 

[msf]

I'm pretty sure this is why Trazodone works so well, it suppresses microglial inflammation. As apparently does LDA.

 

[Violeta]

Is this related to what Dr. Vernon talks about with respect to CRFR1 and CRFR2?


"You were part of the team that conducted a pilot study of a drug called CT38 for ME/CFS patients.
In the 2021 article reporting the results, the team explained their hypothesis that the widespread disruption of systems in patients may be caused by the up-regulation in the brain of a protein called CRFR2.
Could you explain how this might be responsible for ME/CFS symptoms?

Dr. Suzanne Vernon:

The initial observation that transient CRFR2 up-regulation induced symptoms (including fatigue, slowed movement, etc.) came from animal experiments. It turns out that levels of serotonin — a key neurotransmitter that controls most bodily functions — are regulated by CRFR2.
Chronic CRFR2 up-regulation leads to excess serotonin, resulting in numerous symptoms (e.g., fatigue, proprioception [dysfunction], dyspnea, sensory sensitivity, dysautonomia, hypothyroidism, [impaired] glucose control, [impaired] immune function).

Phoenix Rising:

In this study you proposed utilizing "agonist-mediated receptor endocytosis" to down-regulate CRFR2.
What would this treatment involve? Did the results of the trial suggest that this is a viable treatment approach warranting further study?

Dr. Suzanne Vernon:

CT38 is a highly selective agonist that binds to [the receptor called] CRFR2, causing it to down-regulate. If up-regulated CRFR2 causes symptoms, down-regulating CRFR2 should reduce or eliminate symptoms.
An agonist binds to a receptor to initiate a response. In this case, CT38 binds to the receptor CRFR2 and causes the CRFR2 to [be down-regulated by removing it from the surface of the cell in a process called endocytosis].
The CT38 trial in ME/CFS patients supported the hypothesis that CRFR2 was up-regulated and that down-regulating CRFR2 with CT38 was a viable treatment option that deserved further study in a larger trial."