diet, hormones, aging, immune function

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Petr75
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Re: diet, hormones, aging, immune function

Post by Petr75 »

2021 Aug 10
Department of Physiology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
Diosgenin ameliorates cellular and molecular changes in multiple sclerosis in C57BL/6 mice
https://pubmed.ncbi.nlm.nih.gov/34425463/

Abstract

Multiple sclerosis (MS) is especially known as a demyelinating disease of the central nervous system. Current treatments for MS are mostly based on controlling neuroinflammation and there are no treatments to promote the remyelination process at present. Diosgenin is a known herbal anti-inflammatory and antioxidant agent, which has also been shown to stimulate the growth of myelin in vitro. However, there is no or little evidence about diosgenin effects; specially on myelination, neuroprotection and its corresponding mechanisms in vivo in experimental autoimmune encephalomyelitis (EAE) as the most valid experimental model of MS. In this study, the therapeutic effect of diosgenin on clinical signs of EAE, and the corresponding cellular and molecular mechanisms have been examined with emphasis on myelination and neuroprotection mechanisms. EAE was induced using myelin oligodendrocyte glycoprotein (MOG) antigen in C57BL/6 mice. Diosgenin was gavaged (100 mg/kg) daily with the onset of paralysis signs (half tail paralysis) until the 18th post-immunization day in the treatment group. Blood and spinal cord tissue sampling was performed on post-immunization day 18. Lumbar spinal cord inflammation, demyelination, and axonal degeneration were assessed using Hematoxylin and Eosin (H & E), Luxol Fast Blue (LFB), and Bielschowsky's silver staining methods, respectively. Serum and spinal cord tissue level of tumor necrosis factor alpha (TNFα) and tissue levels of matrix metalloproteinase 9 (MMP-9) and interleukin 17 (IL-17) as inflammatory markers, microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A), and activity dependent neuroprotector homeobox (ADNP) as neuroprotective markers were assayed using enzyme linked immunosorbent assay (ELISA) method. The clinical score of EAE in the diosgenin treatment group was significantly reduced compared to the EAE group on days 15 to 18 after induction of the EAE (p < 0.001). Inflammation, demyelination and axonal loss scores also decreased significantly in the diosgenin treatment group compared to the EAE group (p < 0.05). Serum and spinal cord tissue level of TNFα and tissue level of MMP-9 considerably decreased in the diosgenin treatment group in comparison with the EAE group (p < 0.01). Diosgenin treatment had no significant effects on the tissue levels of IL-17, ADNP and MAP1LC3A. Therefore, diosgenin improved the clinical signs of EAE through lowering neuroinflammation, demyelination and axonal degeneration, but did not significantly affect the neuroprotective factors in this study. As a result, diosgenin could be a good candidate for new MS treatment strategies that, in addition to their anti-inflammatory effects, also enhance myelination.
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jimmylegs
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Re: diet, hormones, aging, immune function

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Neural-derived estradiol regulates brain plasticity (2018)
https://www.sciencedirect.com/science/a ... 4621000079

"In addition to be an ovarian hormone, estradiol is a neurosteroid synthesized by neural cells. The brain is a steroidogenic tissue that metabolizes testosterone to estradiol. The last step in the synthesis of estradiol is catalyzed by the enzyme aromatase, which is widely expressed in the brain of male and female animals and humans. Studies that have manipulated the expression or the activity of aromatase have revealed that brain-derived estradiol acts as a neuromodulator and regulates different forms of brain plasticity in male and female animals. The regulation of neuroplastic events by brain-derived estradiol probably participates in the effects of brain aromatase on behavior and cognition."
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Re: diet, hormones, aging, immune function

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17β-Estradiol Reduces Demyelination in Cuprizone-fed Mice by Promoting M2 Microglia Polarity and Regulating NLRP3 Inflammasome (2021)
https://www.sciencedirect.com/science/a ... 2221001585

"... Estrogen produces a beneficial role in animal models of multiple sclerosis (MS). ... In this study, mice were given 0.2% cuprizone (CPZ) for 5 weeks to induce demyelination during which they received 50 ng of 17β-estradiol (EST), injected subcutaneously in the neck region, twice weekly. Data revealed that treatment with 17β-estradiol therapy (CPZ+EST) improved neurological behavioral deficits ... in comparison to untreated CPZ mice. Also, administration of 17β-estradiol caused a decrease in demyelination levels and axonal injury ..."
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Re: diet, hormones, aging, immune function

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Weak correlations between serum and cerebrospinal fluid levels of estradiol, progesterone and testosterone in males (2019)
https://link.springer.com/article/10.11 ... 019-0535-3

"Conclusions
Total steroid levels of estradiol, progesterone and testosterone in CSF and serum of males without neurological disorders were determined. Weak to very weak correlations between CSF and serum were found thus suggesting that concentrations in the periphery do not parallel concentrations in the central compartments. Further research is needed to clarify to what extent and under which conditions serum levels of estradiol, progesterone and testosterone may possibly serve as a biomarker reflecting the respective concentrations in the CSF or in the brain."
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Re: diet, hormones, aging, immune function

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i had to refamiliarize myself with this cuprizone model. i wondered why a copper deficit induced demyelination would be relevant for ms studies. i decided to also refresh my memory as to the nature of copper status in ms patients.

Copper concentration in multiple sclerosis: a systematic review and meta-analysis (2020)
https://www.sciencedirect.com/science/a ... 4820305010

going forward, i still have questions about this cuprizone model.
i will be hoping to find more studies exploring estradiol treatment for actual ms patients.
probably already posted elsewhere here on the forum, but it's where my thoughts have landed just now!

Remyelination therapies: a new direction and challenge in multiple sclerosis (2017)
https://www.nature.com/articles/nrd.2017.115
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

lol i searched on

cuprizone model makes no sense

which returned this result

Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis (2014)
https://www.sciencedirect.com/science/a ... 341400253X

" ...We discuss why cuprizone can be used as a model for multiple sclerosis, schizophrenia and epilepsy."

free full text, guess i have my homework cut out for me :)
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Re: diet, hormones, aging, immune function

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Roles of Progesterone, Testosterone and Their Nuclear Receptors in Central Nervous System Myelination and Remyelination (2020)
https://www.mdpi.com/1422-0067/21/9/3163/htm

" ... We summarize here a recent advancement in the field of myelin biology, to treat demyelinating disorders using the natural as well as synthetic analogs of progesterone and testosterone. ... "

i had found this article earlier, but hadn't dug in. at this point, before reading, i'm skeptical of the merits of the synthetics. having only recently read elsewhere, about the cancer related and other health concerns around synthetic progestins and so on. maybe this article's full text will elaborate on that point. we'll see!
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Re: diet, hormones, aging, immune function

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Systematic review of gender bias in clinical trials of monoclonal antibodies for the treatment of multiple sclerosis (2021)
https://www.sciencedirect.com/science/a ... 5321000086

"Methods
... The following study characteristics were recorded:
... •If there was an analysis of the interaction between hormone replacement therapy AND study drug, included women using hormonal contraceptives. ...

Results
No trial meets any of the other 6 variables:
-analysis of the interaction between hormone replacement therapy and the active drug. ...

Discussion
... The highlight of our work is that it is the first to study the gender differences of the biological drugs used in MS, considered one of the best options in certain types of MS, such as in PPMS, which continues to be developed to improve their efficacy tolerability and safety. ... "
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

Testosterone Loss and Estradiol Administration Modify Memory in Men (2006)
https://www.auajournals.org/doi/abs/10. ... %2900049-2

"Conclusions
Sex steroid loss and replacement have effects on specific cognitive processes in older men. Furthermore, estrogen has the potential to reverse the neurotoxic effects on memory performance caused by androgen deprivation."
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

may take some time to reconcile the above with:

Endogenous Estradiol and Testosterone Levels Are Associated with Cognitive Performance in Older Women and Men (2002)
https://www.sciencedirect.com/science/a ... 6X02917708

" ... In men the only significant association was a negative correlation between testosterone and verbal fluency (r = −0.38, P < 0.05). The associations observed in this small study support the notion that estradiol is protecting verbal memory and possibly also frontal lobe mediated functions in older women. In contrast to the positive findings in women endogenous sex steroids do not appear to be closely linked to better cognition in older men."
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

ok, noted: adding a daily progestin (!) and weekly (?!) E2 doesn't correct for dramatic post partum drop in E3. check.
still all very new matl for me, but definitely seems like a counterintuitive approach at this point.

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study (2016)
https://journals.sagepub.com/doi/abs/10 ... 8520978218

slow inclusions - makes sense, from here :)

i wish someone would publish findings from a new estriol rct. and i want to know how estriol does with and without meds like copaxone, and fwiw i am more interested in its effects on remyelination if any, than on cognition.

and on that note,

Is it time to conduct phase 3 clinical trials of sex hormones in MS – Commentary (2018)
https://journals.sagepub.com/doi/full/1 ... 8518786071

"we still lack a sensitive and specific measure of remyelination."

cited by nobody. boo.
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

i remember having made the renal connection to vitamin d status at least ten years ago. very interesting to be circling back in on it now

Influence of estrogen on renal vitamin D hydroxylases and serum 1alpha,25-(OH)2D3 in chicks (1978).
https://journals.physiology.org/doi/abs ... 235.3.E338
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

jimmylegs wrote: Sun Aug 29, 2021 10:43 am lol i searched on

cuprizone model makes no sense

which returned this result

Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis (2014)
https://www.sciencedirect.com/science/a ... 341400253X

" ...We discuss why cuprizone can be used as a model for multiple sclerosis, schizophrenia and epilepsy."

free full text, guess i have my homework cut out for me :)
sep 10:. still have not done said homework. still wondering how treatments applied in a demyelination scenario secondary to copper deficiency would be applicable to real life human ms.
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Re: diet, hormones, aging, immune function

Post by jimmylegs »

off to the neuro tomorrow morning. i know i'm supposed to be making a decision about ocrevus, but i'm more interested in asking questions about hormones! yea the ones that make no one rich. wish me luck lol
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awesome! Re: diet, hormones, aging, immune function

Post by jimmylegs »

lol oh yeah, that. ^
good news, got a referral.
phone appointment coming up at the end of march....

in the meantime... i LOVE this one:

Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy (2021)
https://alz-journals.onlinelibrary.wile ... trc2.12174
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