2017 study: Pathogenic implications of Fe & Zn in MS lesions

A forum to discuss research on the origins of MS and its development.

2017 study: Pathogenic implications of Fe & Zn in MS lesions

Postby jimmylegs » Thu Dec 07, 2017 6:08 am

Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions (2017)
https://link.springer.com/article/10.10 ... 017-1696-8
Abstract
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis. We found that the distribution of iron and zinc is heterogeneous in MS plaques, and with few remarkable exceptions they do not accumulate in chronic MS lesions. We show that brain iron tends to decrease with increasing age and disease duration of MS patients; reactive astrocytes organized in large astrogliotic areas in a subset of smoldering and inactive plaques accumulate iron and safely store it in ferritin; a subset of smoldering lesions do not contain a rim of iron-loaded macrophages/microglia; and the iron content of shadow plaques varies with the stage of remyelination. Zinc in MS lesions was generally decreased, paralleling myelin loss. Iron accumulates concentrically in a subset of chronic inactive lesions suggesting that not all iron rims around MS lesions equate with smoldering plaques. Upon degeneration of iron-loaded microglia/macrophages, astrocytes may form an additional protective barrier that may prevent iron-induced oxidative damage.

thinking back to forum chats going back close to a decade ago now...:

Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins (2008)
https://www.ncbi.nlm.nih.gov/pubmed/18073202
Abstract
One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

a small study, and i'd rather see serum ferritin than serum iron, but still interesting

Serum level of iron, zinc and copper in patients with multiple sclerosis (2013)
http://jmj.jums.ac.ir/article-1-22-en.pdf
Introduction:
Multiple sclerosis (MS) is one of the most common neurologic disorders. It appears that in addition to the common risk factors, there may be other factors, such as serum level of trace elements, which affect the development or course of the disease. The aim of this study was to evaluate the serum levels
of iron, zinc and copper in patients with MS and compare them with the control group.
Materials and Methods:
In this study, serum levels of iron, zinc and copper were determined in 25 patients with MS and compared with those of 25 healthy individuals matched with age and sex. Data were analyzed in SPSS, version17 using statistical descriptive methods (mean- percentage, SD) and t-test
Results:
In this study, there were 9 males in the case and control groups and the rest were female. The mean age of the patients was 28 ± 3.44 years for men and 24 ± 2.55 years for women. Mean serum iron levels were significantly elevated in MS patients (127.04 ± 34.67) compared to these levels in the
control group (103.95 ± 33.81). Mean serum zinc levels were significantly decreased in MS patients (10.92 ± 2.114) as compared to these levels in the control group (14.05 ± 3.2). Also, mean serum copper levels were significantly decreased in MS patients (88.58 ± 19.56) compared to the levels in
the control group (110.37 ± 37.1).
Conclusion:
The findings of this study show that serum levels of Iron, Zinc and Copper in patients with MS are different from those in normal population.

i found that when i fixed my zinc deficiency, copper did at first jump up as well. was nervous originally, but ended up okay with it increasing, as long as the level stays ideally just below the target zinc level in serum
odd sx? no dx? check w/ dietitian
DRI=MINIMUM eg bit.ly/1vgQclQ
99% don't meet these. meds/lifestyle can affect levels
status can be low in ms & other cond'ns
'but my results are normal'. typical panels don't test all
deficits occur in 'normal' range
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Re: 2017 study: Pathogenic implications of Fe & Zn in MS les

Postby frodo » Thu Dec 14, 2017 1:13 am

i found that when i fixed my zinc deficiency, copper did at first jump up as well. was nervous originally, but ended up okay with it increasing, as long as the level stays ideally just below the target zinc level in serum


There are too much reports about iron and zinc to be a coincidence. Thanks for the summary.
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