Myelin lipid metabolism and its role in myelination and myelin maintenance, 2022, Barnes-Vélez et al

Discussion in 'Neurological diseases' started by SNT Gatchaman, Mar 5, 2023.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Myelin lipid metabolism and its role in myelination and myelin maintenance
    Barnes-Vélez JA, Aksoy Yasar FB, Hu J

    Myelin is a specialized cell membrane indispensable for rapid nerve conduction. The high abundance of membrane lipids is one of myelin's salient features that contribute to its unique role as an insulator that electrically isolates nerve fibers across their myelinated surface. The most abundant lipids in myelin include cholesterol, glycosphingolipids, and plasmalogens, each playing critical roles in myelin development as well as function.

    This review serves to summarize the role of lipid metabolism in myelination and myelin maintenance, as well as the molecular determinants of myelin lipid homeostasis, with an emphasis on findings from genetic models. In addition, the implications of myelin lipid dysmetabolism in human diseases are highlighted in the context of hereditary leukodystrophies and neuropathies as well as acquired disorders such as Alzheimer's disease.

    PubMed | Link | PDF
     
  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Open access. I'll summarise and highlight the text, with links.

    CGT - cerebroside galactosyl-transferase
    CNS - central nervous system
    ER - endoplasmic reticulum
    GalC - galactocerebride (aka galactosylceramide)
    GSL - glycosphingolipid
    mTOR - mammalian target of rapamycin
    mTORC - mammalian target of rapamycin complex (1 and 2)
    OL - oligodendrocyte (CNS)
    OPC - oligodendrocyte precursor cell
    PE - phosphatidylethanolamine
    PNS - peripheral nervous system
    PPAR - peroxisome proliferator-activated receptor
    QKI - quaking (homologue)
    SC - Schwann cell (PNS)
    SREBP - sterol regulatory element-binding protein

    ---
     
    Last edited: Mar 5, 2023
  3. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  4. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Paranodal loops - see Node of Ranvier: "The internodal glial membranes are fused to form compact myelin, whereas the cytoplasm-filled paranodal loops of myelinating cells are spirally wrapped around the axon at both sides of the nodes. This organization demands a tight developmental control and the formation of a variety of specialized zones of contact between different areas of the myelinating cell membrane."
     
  5. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  6. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    SNT Gatchaman Senior Member (Voting Rights)

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    SNT Gatchaman Senior Member (Voting Rights)

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  10. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  11. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  12. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Concluding —

     
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  13. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    So my questions would be: if lipid metabolism is systemically deranged, could that be causing impairments to myelin structure? Those impairments would not be at the level seen in eg MS or the genetically-determined leukodystropies; instead they could produce much more subtle changes to myelin and nodal structure and composition.

    I would expect these sorts of effects could very well cause time- and spatial-varying symptoms due to non-deterministic effects on conduction velocities or interaxonal cross-talk. As outlined above, myelin is dynamic and dependent on lipid metabolism with some components having turnover of weeks. That could also cause non-fixed neurological deficits, that might defy a simplistic neurological model (see FND, functional motor, sensory and seizure disorders).
     
  14. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    Plasmalogens were decreased in ME/CFS. Low plasmalogens are associated with neurodegeneration and cognitive impairment.
     
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  15. Andy

    Andy Committee Member

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  16. Andy

    Andy Committee Member

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  17. Creekside

    Creekside Senior Member (Voting Rights)

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    Did you come across any mention of the effects of circulating fatty acids? I've become intolerant of fibre metabolites, possibly propionate, and I can certainly imagine that the local availability of fatty acids could affect how the membranes (or mylelin) is assembled. Maybe, for example, a certain ion transport pore is formed when x molecules of propionate are collected at a point on the forming membrane.
     
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  18. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  19. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Not sure about the idea referenced in the poster from #16 of "preventing ATP production by myelin", but the idea that the lipid structure in myelin can become deranged could be a good explanation for the observation of apparent disease onset following major surgery (typically framed as due to "stress"). GAs have been used safely in millions for decades, but I can imagine a situation of regionally impaired myelin microstructure that is compensated, so subclinical in terms of recognised symptoms, but the subsequent metabolic insult tips beyond compensation/homeostasis.

    Also as a summary, the reference to the sympathetic nervous system being unmyelinated doesn't seem quite right. As far as I know the ANS is myelinated centrally, but many of the post-ganglionic fibres aren't. BP control under anaesthesia is important and multi-factorial and I'm sure the ANS would be a large part of that. (Mechanical ventilation is already required due to muscle relaxants paralysing the respiratory muscles.)
     
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