Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Paper on cobalamin, prions, TNF-alpha, and Neuropathies?

Discussion in 'Other Health News and Research' started by voner, Jan 22, 2013.

  1. voner

    voner Senior Member

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    This might be of interest to somebody out there. Italian authors.

    http://www.sciencedirect.com/science/article/pii/S0300908413000035

    Cobalamin and normal prions: A new horizon for cobalamin neurotrophism

    Abstract
    It is known that cobalamin (Cbl) deficiency damages myelin by increasing tumor necrosis factor (TNF)-α and decreasing epidermal growth factor (EGF) levels in rat central nervous system (CNS), and affects the peripheral nervous system (PNS) morphologically and functionally. It is also known that some polyneuropathies not due to Cbl deficiency are connected with increased TNF-α levels, and that various cytokines (including TNF-α) and growth factors regulate the in vitro synthesis of normal prions (PrPCs). Given that there is extensive evidence that PrPCs play a key role in the maintenance of CNS and PNS myelin, we investigated whether the PrPC octapeptide repeat (OR) region is involved in the pathogenesis of rat Cbl-deficient (Cbl-D) polyneuropathy. After intracerebroventricularly administering antibodies (Abs) against the OR region (OR-Abs) to Cbl-D rats to prevent myelin damage and maximum nerve conduction velocity (MNCV) abnormalities, and PrPCs to otherwise normal rats to reproduce PNS Cbl-D-like lesions, we measured PrPC levels and MNCV of the sciatic and tibial nerves. PrPC and TNF-α levels were increased in sciatic and tibial nerves of Cbl-D and saline-treated rats, and the OR-Abs normalized the myelin ultrastructure, TNF-α levels, and MNCV values of the sciatic and tibial nerves of Cbl-D rats. The same peripheral nerves of the otherwise normal PrPC-treated rats showed typical Cbl-D myelin lesions, significantly increased TNF-α levels, and significantly decreased MNCV values. These findings demonstrate that Cbl deficiency induces excess PrPCs and thereby excess OR regions, which seem to be responsible for the PNS myelin damage, as has recently been found in the case of CNS myelin damage [66]. Furthermore, excess TNF-α is also involved in the pathogenesis of Cbl-D polyneuropathy. In conclusion, we have extended the list of prion diseases by adding one caused by excess PrPCs and the polyneuropathies related to excess TNF-α.
     
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  2. lansbergen

    lansbergen Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/23146213

    J Clin Neurosci. 2013 Jan;20(1):134-8. doi: 10.1016/j.jocn.2012.08.004. Epub 2012 Nov 10.
    Cobalamin as a regulator of serum and cerebrospinal fluid levels of normal prions.

    Scalabrino G, Veber D, Briani C, Milani S, Terralavoro A, Brenna S, Valenti L, Silani V, Morelli C, Peracchi M.
    Source

    "Città Studi" Department, Laboratory of Neuropathology, University of Milan, Milan, Italy. Electronic address: giuseppe.scalabrino@unimi.it.
    Abstract

    We have previously demonstrated that the concentration of normal prion proteins (PrP(C)) is increased in the serum and cerebrospinal fluid (CSF) of rats deficient in vitamin B(12) (cobalamin, Cbl). In this study, we investigated whether similar increases also occur in the serum and CSF of patients deficient in Cbl (Cbl-D), and whether the increase in serum levels can be corrected by Cbl therapy. The study involved two sample populations. The first consisted of 45 patients (13 patients with pernicious anemia [PA], 19 with other forms of anemia, and 13 healthy controls); and the second, 68 patients (five with subacute combined degeneration [SCD], 18 with amyotrophic lateral sclerosis, 22 with multiple sclerosis [MS], and 23 neurological controls). Serum PrP(C) levels were measured using an enzyme-linked-immunosorbent-assay before as well as after Cbl therapy. The mean serum PrP(C) levels in patients with PA were significantly higher than those of the controls (p=0.0017) but normalized after Cbl therapy; there was no significant change in the patients with other forms of anemia. Mean CSF PrP(C) levels in the patients with SCD were significantly higher than in the neurological controls (p<0.03). The serum and CSF PrP(C) levels of patients with PA and those with SCD were correlated significantly with serum (p=0.004) and CSF (p=0.0018) Cbl levels. In patients with MS, CSF PrP(C) concentrations were significantly lower than those of the controls regardless of their CSF Cbl levels. We found a correlation between Cbl and PrP(C) levels in the serum and CSF of Cbl-D patients, which suggests that Cbl may regulate the PrP(C) levels in the serum and CSF in humans.
     
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  3. kurt

    kurt Senior Member

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    Syracuse, Utah, USA
    Thanks for posting these studies, although this seems a bit confusing, I think it looks significant. Too bad they did not test CFS patients, or at least Alzheimer's or Parkinson's, since our protein signatures are related. Probably this shows yet another down-stream problem that can result from methylation defects.

    Here is an earlier study with normal prion proteins, in Alzheimer's, where their presence correlates with the disease.

    http://www.nature.com/news/2009/090225/full/news.2009.121.html

    So this might be interesting, if some researcher can find a connection now between Alzheimer's and cobalamin levels.
     

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