Estrogen Promotes Remyelination in Adult Brains of MS Mice, Study Shows

Estrogen Promotes Remyelination in Adult Brains of MS Mice, Study Shows

Giving estrogen to two different adult mouse models of multiple sclerosis (MS), including the experimental autoimmune encephalomyelitis (EAE) model, promoted remyelination, a new study shows.

Exposure to the hormone affected gene activity in oligodendrocytes, tricking them into producing myelin (the fatty substance that protects nerve cells, and that is destroyed in MS). This process appears to mimic the in utero development of the brain, when the fetus is exposed naturally to estrogen in the mother’s blood.

The study, “Cell-specific and region-specific gene expression in multiple sclerosis models: Focus on oligodendrocytes during remyelination” was published in the journal PNAS.

The brain is a complex organ composed by different cell types that organize in different clusters through the organ. As a consequence, the activity of genes in the brain is patterned.

Researchers at UCLA in California analyzed the brain of five MS patients to assess the disease’s impact on gene activity across six different brain regions, when compared to five age- and sex-matched healthy controls. They did the same analyses for seven cell types in the brain.

The analysis identified two brain regions — the corpus callosum, which links the two sides of the brain, and the optic chiasm, a region controlling vision — and one cell type, the oligodendrocytes, as the most significantly affected by MS.

Researchers then investigated further how the gene pattern in oligodendrocytes in one of the major regions affected by MS, the corpus callosum, changed during remyelination after chronic loss of myelin in vivo using a mouse model of MS. The animals were fed with cuprizone, a copper-binding toxin that kills oligodendrocytes and causes demyelination in brain areas, including the corpus callosum. Replacement of cuprizone with normal food is followed by remyelination.

The team performed the same analysis in the EAE model, the most widely used model of MS.

Researchers also tried to boost remyelination by treating the adult mice with an estrogen receptor beta compound, previously shown to have neuroprotective effects by stimulating natural myelination.

They found that as myelin was repaired naturally, oligodendrocytes turned on genes promoting the production of cholesterol. Treatment with the estrogen receptor beta also increased cholesterol production and enhanced remyelination in the cuprizone MS model.

During embryonic development, oligodendrocytes in the developing fetus are exposed to high levels of estrogen, the natural binding partner of estrogen receptors, present in maternal blood. “We hypothesize that remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination by targeting cholesterol homeostasis,” the researchers wrote.

“In conclusion, discovery of cell-specific and region-specific molecular signatures of disease in preclinical models can provide novel targets tailored for each neurological pathway in MS, as a strategy to optimize neuroprotective treatment development,” they added.

17 comments

  1. Collette Howell says:

    As a 72 year old female with a progressive version of MS and one who is struggling with cognitive impairment, I am anxious to talk with my Dr about going back on HRT. I do not have time to wait for this potential treatment to be confirmed as effectIve.

    • Charlotte Hart says:

      Hi Collette, I’ve recently been wondering how MS symptoms are affected by the menopause. Can you please give me your comments about how it has affected you. Many thanks. Charlotte

      • Ellen says:

        @Charlotte Hart I can’t say the MS was affected by menopause. I was on HRT as soon as I was in very early estrogen decline and about 25 years later I am still on it. I haven’t had much in way of symptoms. I was 57 when I had one major set back and was diagnosed and when on Copaxone. That was 13 years ago. So whether it was the DMT and or Hormone Therapy of all the vitamin suppliments or just luck, I don’t know.

    • Joanne Perkins says:

      Amen to that, sister! I’m 58, and have struggled over 30 years with this disease, watching my ability
      physically, cognitively and emotionally decline while my fatigue is ever increasing. It makes it hard to fight this battle; but, let me encourage you to press on, we’re in this together. Please look into “bio-identical” methods of hormone replacement, opting for estriol over estradiol (the synthetic version of estrogen).

  2. Heidi says:

    Have there been any comparisons of MS women in HRT versus those not? Also researchers could look into comparing MS progression in women who have early, normal and late menopause. I think there is a hormone link. I was like a non-MS person when I was pregnant for example and MS is more prevalent in women.

  3. Patricia O'Connor says:

    It’s about time! Wrote my book Hereditary Hemochromatosis? Years ago and on page 1 talked about iron found in autopsies of MS brains! Interesting connection?

    Written by Tricia O’Connor

    P.S. My friend Dr. Piche and other doctors at UWO believe the cause of MS is epigenetics and UVB.

    I’ll be rich when I’m dead my Dad says!

  4. Ellen says:

    I have been on HRT since my mid 40s; I am 71 now and still on it. My MS has not progressed. I was on Copaxone for 12 years. I just came off it last month; there have been articles about maybe not needing DMT after a certain age and after being on DMT for about 12 years and having little in way of symptoms. I always wonder if I have been better off b/c I take the hormones. I think there should be more studies on this. Hopefully I’ll continue to do well without the DMT. Time will tell.

  5. Ellen says:

    I I conmented here but didn’t show up. I have been on HRT since I was in mid 40’s. I am now 71 and still on HRT. I have known about my MS for last 13 years and was on Copaxone for 13 years. I am not progressive. I came of of my DMT last month as I have read articles about coming off medication at an older age for some people. I wonder if HRT was has helped me not be progressive but don’t know for sure. Time will tell. I will have another MRI in 6 months. So far no active lesions 13 years ago and this year.

  6. I often thought about this I have hypothyroidism also…it was hard for me to get pregnant. I felt awesome when I was pregnant too. Both pregnancies I needed progesterone to keep the pregnancies.

    • Joanna H says:

      For a period of 3 months, my 75 year-old mother took anti-estrogen meds as part of the treatment for Stage 0 breast cancer. The meds caused her to suffer increased joint pain and exhaustion. She has been off the meds for over a month with no improvement in the level of joint pain. After reading this article, I am wondering if demyelination could have occurred and, if so, will her body be able to regenerate the myelin as her estrogen levels normalize?

  7. Dawn says:

    I think they are on to something with the estrogen. I had an incident in January and I was flooded with estrogen. My body lit up like a Christmas Tree. I felt like every cell in body had been rejuvenated. I am now back to walking 5 miles a day, sleeping better, moods improved, inflammation is way down. I am thankful for this article because until I read it I thought I had gone crazy but apparently my hunch on the estrogen might be exactly what caused my sudden remission. I haven’t felt this good in years!

  8. Barbara says:

    All the comments are by women. Any men have this therapy? How has it effected you? My boyfriend has MS. What is the link with cholesterol? He is on cholesterol meds. Could those medications be causing more demylenation?

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