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Part 2: Brain Cells Making us Sick? Messed up microglia could be driving symptoms

Discussion in 'Phoenix Rising Articles' started by Simon, Jun 1, 2014.

  1. Esther12

    Esther12 Senior Member

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    Thanks Simon.

    Low dose naltrexone is something I've heard people mention for CFS for ages, so I was a bit surprised that my googling didn't bring up any research. I'd have thought that we'd have to be dealing with subsets again as if LDN was significantly helpful for the majority of people surely there'd be more positive word on the grapevine.
     
    Simon likes this.
  2. RYO

    RYO

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    Overall, very interesting concepts re: role of microglia dysfunction in CFS / ME. Similar theory raised in role of vagus nerve in CFS / ME. However, there is "missing piece of puzzle" for those of us that have severe localized muscle weakness and pain. It is true that generalized muscle pain and weakness characterize "sickness behavior" but I have never experienced severe localized muscle symptoms (ie hip girdle area) with previous exposure to illnesses such as influenza. Nor does it explain the muscle fasciculations I have experienced for last 2 years since my initial acute illness.

    I have always described to my friends that after my acute illness, it seemed I aged overnight. I went from feeling like someone in their late 30's to a debilitated 90 year old. Some recent news about anti-aging and parabiosis sparked a question re: link between microglia cells and skeletal muscle function.

    Does anyone have any information about which cell lines produce GDF11? A study examining whether CFS / ME patients have lower GDF11 levels vs healthy controls would be interesting.
     
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  3. bmoberg337

    bmoberg337

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    Similar studies have been conducted using animal models for quite sometime now. These studies particularly focused on stress induced changes on microglial and consequential release of pro-inflammatory cytokines, mainly IL-1beta.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788324/

    It was found in animal models that this response could be blunted by administering Minocycline (anti-inflammatory, commonly used to treat acne). I searched these forums and found a thread form 2010 talking about mixed results using minocycline.

    http://forums.phoenixrising.me/index.php?threads/minocyclin.7983/
     
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  4. user9876

    user9876 Senior Member

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    Here is an article talking about the debate over the accuracy animal research and Microglia. They suggest that there are quite a few differences in the way mice microglia bind to different things.

    http://phenomena.nationalgeographic.com/2014/04/07/microglia-in-mice-and-men/
     
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  5. Simon

    Simon

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    Thanks, that's very interesting.

    For those that want more, this is the study: Acute and Chronic Stress-Induced Disturbances of Microglial Plasticity, Phenotype and Function
    As @searcher pointed out, the problem is that microglial inhibitors aren't well understood, and usually have other functions too, so it's hard to read too much into results from one inhibitor. I think @Esther12 mentioned similar mixed results with LDN
    edit: Here's that comment from Dr Younger:
     
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  6. Leopardtail

    Leopardtail Senior Member

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    It will be interesting to see the results of that study... on microglia
     
  7. Leopardtail

    Leopardtail Senior Member

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    PS Where is part one of this?
     
  8. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    There's a link to it at the top of the page.
     
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  9. Simon

    Simon

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    First, here's a very readable homage to microglia, the subject of this blog
    Best Cells Ever – (microglia)

    Brain Cells Making us Sick? The microglia connection in ME/CFS & Fibromyalgia

    Thanks, really interesting stuff: Microglia in Mice and Men
    ....
    This is an important debate, but it may also be that animal model 'therapies' don't work in humans beccause the original animal work is duff, which is exactly what's argued here (and elsewhere):

    Preclinical research: Make mouse studies work : Nature News & Comment
    The published data look great - but didn't replicate in animal model testing either:

    [​IMG]
     
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  10. osisposis

    osisposis

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    FASEB J. 2012 Aug;26(8):3103-17. doi: 10.1096/fj.11-197194. Epub 2012 Apr 19.
    Microglia and mast cells: two tracks on the road to neuroinflammation.
    Skaper SD1, Giusti P, Facci L.
    Author information
    Abstract
    http://www.ncbi.nlm.nih.gov/pubmed/22516295


    The Mast Cell: A
    Cell for All Seasons

    Theoharis C. Theoharides, MS, PhD, MD, FAAAAI

    http://www.mastcellmaster.com/documents/2014-04/TCT-Research-Overview-3-12-14.pdf


    Immunology. 2014 Mar;141(3):314-27. doi: 10.1111/imm.12170.
    Mast cells, glia and neuroinflammation: partners in crime?
    Skaper SD1, Facci L, Giusti P.
    Author information
    Abstract

    http://www.ncbi.nlm.nih.gov/pubmed/24032675




    Mast cells in the brain: evidence and functional significance
    http://www.sciencedirect.com/science/article/pii/0166223696818637


    Mast cells on the mind: new insights and opportunities
    http://www.sciencedirect.com/science/article/pii/S0166223613001124


    Mast cells, microglia and brain inflammation

    http://www.autismfile.com/science-research/mast-cells-microglia-and-brain-inflammation
     
    Last edited: Jun 8, 2014
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  11. osisposis

    osisposis

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    Leptin, a neuroendocrine mediator of immune responses, inflammation, and sickness behaviors
    http://www.sciencedirect.com/science/article/pii/S0018506X12001286

    Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice


    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287967/


    Human mast cells express leptin and leptin receptors.
    http://www.ncbi.nlm.nih.gov/pubmed/19241089


    Allergy. 2013 Jan;68(1):8-15. doi: 10.1111/all.12043. Epub 2012 Oct 16.
    Do mast cells link obesity and asthma?

    http://www.ncbi.nlm.nih.gov/pubmed/23066905


    Leptin and Mast Cells: A Novel Adipoimmune Link
    http://journals.tubitak.gov.tr/medical/issues/sag-01-31-6/sag-31-6-22-0102-7.pdf
     
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  12. osisposis

    osisposis

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  13. Wayne

    Wayne Senior Member

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    Thanks Simon...
     
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  14. Simon

    Simon

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  15. Simon

    Simon

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    A new paper has just been published taking from a rat model that provides support for microglial activation leading to fatigue, as proposed in several of the theories explored in this blog.

    In a nutshell, it shows that poly-I:C - which activates the immune system (acts like a super-charged RNA virus), activates microglia long-term, and leads to them producing the cytokine Interleukin-!b. Importantly, their study indicates that Interleukin-1b then acts on astrocytes to trigger fatigue due to over-expression of serotonin transporters.
    Astrocytes are not neurones, but another type of brain cell that has many important functions, including some immune roles.
     
  16. alex3619

    alex3619 Senior Member

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    I have long been interested in lipopolysaccharide activation of immune responses in ME. I wanted to write a blog on it but my serious blogs are on hold till I improve. LPS has been found elevated in ME patients, though I do not know how reliable the finding is. LPS is a superantigen. It can massively change immune responses. That is because, I think, the immune system reacts to LPS in the blood as though there were a massive bacterial infection. So LPS getting through the gut wall and then the liver detox could easily induce big immune changes on an ongoing basis, and its even possible this is more common after eating ... right when leptin levels might change. This is just speculation, but I keep thinking about it.

    The microglial theory is looking more and more interesting over time.
     
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