Selective translocator protein (TSPO) agonists

EddieB

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After the dramatic reduction of symptoms yesterday from the Ativan, has me thinking that possibly some type of neuro Med could be helpful, even short term. However, there seems to paradox with most, that they have the potential side effect of weakening the esophagus sphincter. And also for some, the fear of dependency.

So far, the only ones that seem safer are LDN and buspirone. I’m not entirely certain on the LDN, but buspirone is listed as strengthening to esophagus. More study needed.
 

ljimbo423

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After the dramatic reduction of symptoms yesterday from the Ativan, has me thinking that possibly some type of neuro Med could be helpful, even short term.
It sure seems like it. Even if you need to take Ativan, maybe you can take it say 2-3 days a week to avoid dependence. Then find something like LDN or buspirone to take on the days in between.

You might need to think outside the box to get a handle on this.:)
 

EddieB

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It sure becomes a chicken/ egg thing, as to what is causing what. I’m certain my gut bacteria/ balance is screwed up, but if the gut is consistently under neurological stress, well that’s not going to make for a healthy environment. I’m not under much external stress, but my guts are in a near constant state of tension. And I have at times struggled with anxiety/ panic attacks over my entire life. In looking back, the amitriptlyne I was on for a few years may have been providing some stability, but the fatigue/ out of breath side effects were awful. As you know, I’ve tested for everything possible, and tried all the natural methods, with no help. Proceeding with caution...thanks!
 
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ljimbo423

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It sure becomes a chicken/ egg thing, as to what is causing what. I’m certain my gut bacteria/ balance is screwed up, but if the gut is consistently under neurological stress, well that’s not going to make for a healthy environment. I’m not under much external stress, but my guts are in a near constant state of tension. And I have at times struggled with anxiety/ panic attacks my entire life.
It could have very easily been me saying these very same things!! Good luck going forward!
 

Pyrrhus

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I just saw this paper and thought of this thread. It discusses the TSPO binding affinity of diazepam inducing microglia to cause cognitive impairment.
From the abstract:
Here we report that diazepam, a widely prescribed benzodiazepine, impairs the structural plasticity of dendritic spines, causing cognitive impairment in mice. Diazepam induces these deficits via the mitochondrial 18 kDa translocator protein (TSPO), rather than classical γ-aminobutyric acid type A receptors, which alters microglial morphology, and phagocytosis of synaptic material. Collectively, our findings demonstrate a mechanism by which TSPO ligands alter synaptic plasticity and, as a consequence, cause cognitive impairment.
:monocle: So does this simply mean that benzodiazepines are TSPO agonists that activate the tissue-resident macrophages known as microglia, which then attack neuron growth?

:monocle: If so, does this mean that etifoxine, which appears to calm the tissue-resident macrophages, is actually then a TSPO antagonist?
 
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RYO

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I recently came across the article discussing how benzodiazepines may lead to cognitive impairment.

My interpretation is that neuro-inflammation may be mediated by over active microglia in MECFS after viral insult. Some patients benefit with benzodiazepines because they reduce effect of microglia on surrounding neurons over time (by activating TSPO receptor which leads to microglial activation with subsequent loss of dendritic spines). However the effects are global and there may be specific areas of the brain where benzodiazepines still cause side effects such as dizziness or altered motor function via cerebellum. I wish someone could tie this back to the (BOLD - Blood Oxygen Level Dependant) MRI studies that show increased activity in default mode network of the brain after exercise challenge. Perhaps they could repeat the (BOLD) MRI in MECFS patients after they have been on fixed dose of benzodiazepines for a certain period of time to see the effects on post exercise activity of the default mode network. Also I would be interested in looking at the effect of low dose benzodiazepines vs “normal” doses.

Given what we know about long covid, are the brain changes caused by microclots or some other virus induced neuropathology. Are there more dendritic spines in MECFS patients due to deactivation of TSPO receptor?

Also how does this potentially relate to MECFS patients who suffer from chronic muscle pain. Are there cells similar to glial cells in/near muscle tissue, neuromuscular junction or at the spinal level that might explain chronic pain or lower pain/temperature threshold.
 
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