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Cytokines regulate expression of Norepinephrine Transporter

Discussion in 'Latest ME/CFS Research' started by ramakentesh, Jul 4, 2012.

  1. ramakentesh

    ramakentesh Senior Member

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    Can Inflammatory illness or inflammation cause POTS?

    Functional noradrenergic transmission requires the coordinate expression of enzymes involved in norepinephrine (NE) synthesis, as well as the norepinephrine transporter (NET) which removes NE from the synapse. Inflammatory cytokines acting through gp130 can suppress the noradrenergic phenotype in sympathetic neurons. This occurs in a subset of sympathetic neurons during development and also occurs in adult neurons after injury. For example, cytokines suppress noradrenergic function in sympathetic neurons after axotomy and during heart failure. The molecular basis for suppression of noradrenergic genes is not well understood, but previous studies implicated a reduction of Phox2a in cytokine suppression of dopamine beta hydroxylase. We used sympathetic neurons and neuroblastoma cells to investigate the role of Phox2a in cytokine suppression of NET transcription. Chromatin immunoprecipitation experiments revealed that Phox2a did not bind the NET promoter, and overexpression of Phox2a did not prevent cytokine suppression of NET transcription. Hand2 and Gata3 are transcription factors that induce noradrenergic genes during development and are present in mature sympathetic neurons. Both Hand2 and Gata3 were decreased by cytokines in sympathetic neurons and neuroblastoma cells. Overexpression of either Hand2 or Gata3 was sufficient to rescue NET transcription following suppression by cytokines. We examined expression of these genes following axotomy to determine if their expression was altered following nerve injury. NET and Hand2 mRNAs decreased significantly in sympathetic neurons 48 h after axotomy, but Gata3 mRNA was unchanged. These data suggest that cytokines can inhibit NET expression through downregulation of Hand2 or Gata3 in cultured sympathetic neurons, but axotomy in adult animals selectively suppresses Hand2 expression.

    http://www.ncbi.nlm.nih.gov/pubmed/21241805
     
  2. adreno

    adreno Homo neanderthalensis

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    Personally, whenever I have an acute infection, my orthostatic intolerance worsens. This would fit with the above hypothesis.
     
  3. ramakentesh

    ramakentesh Senior Member

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    yeah many report this. So its interesting.
     
  4. ramakentesh

    ramakentesh Senior Member

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    Might even explain a model of CFS that starts with CFS type fluey fatigue from chronic elaboration of pro inflammatory cytokines that eventually leads into POTS with potential modulation of NET gene expression??
     
  5. adreno

    adreno Homo neanderthalensis

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    But does this theory explain all types of POTS, even adrenergic POTS?

    Olive leaf extract increase NET activity BTW. It makes my POTS worse.
     
  6. xks201

    xks201 Senior Member

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    Adrenergic pots most likely involves norepinephrine. This is a very important study that has potential to explain many CFS cases.
     
  7. GcMAF Australia

    GcMAF Australia Senior Member

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  8. GcMAF Australia

    GcMAF Australia Senior Member

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    Hi,
    From this Dr Lewis who has a CFS clinic
    http://www.cfsdiscovery.com.au/
    He looks at food intolerance and gut bacteria.
    • Increased Intestinal Permeability

    • There is a relationship between all these processes causing gastrointestinal immunological and neurotoxic symptoms.
    The Clinic will email a summary of this.​
    Most/All patients show improvement after consideration of these factors.​
    Best Regards​
    GcMAF​
     

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