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Novel complementary effects of estrogen treatment in multiple sclerosis

Date:
December 28, 2017
Source:
University of California - Los Angeles
Summary:
A study reveals the cellular basis for how the hormone protects against damage to the central nervous system.
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A study by UCLA researchers reveals the cellular basis for how the hormone estrogen protects against damage to the central nervous system in people with multiple sclerosis (MS). The researchers found that estrogen treatment exerts positive effects on two types of cells during disease -- immune cells in the brain and also cells called oligodendrocytes. Complementary actions on these two types provide protection from disease.

Multiple sclerosis is a chronic autoimmune, neurodegenerative disease marked by visual impairment, weakness and sensory loss, as well as cognitive decline. These symptoms emerge when inflammatory immune cells destroy the myelin sheath that surrounds nerve processes called axons. Loss of that protective insulation disrupts electrical communication between nerve cells.

The third trimester of pregnancy has been previously shown to reduce relapse rates by approximately 70 percent as compared to before pregnancy, and other studies have shown benefit over the long term due to multiple pregnancies. An estrogen unique to pregnancy that is made by the fetus and placenta has been proposed by Dr. Rhonda Voskuhl and colleagues to mediate this pregnancy protection in both the MS mouse model as well as in two successfully completed clinical trials of estriol treatment in MS patients.

How that happens has remained a critical question. Voskuhl, who led the latest study, reported mouse studies showing that estrogen protected the brain from damage by activating a protein called estrogen receptor beta (ERb). Her new research identifies which cells within the brain are mediating this protective effect.

The researchers first genetically eliminated ERb in either immune cells of the brain or in oligodendrocytes, the cells that make the myelin sheath, as a way of making cells unresponsive to estrogen during the MS like disease in mice. They then treated mice without or with ERb in these cells to ask if disease protection was lost or not. Loss of protection during treatment meant that the treatment was acting on the cell that had the receptor removed. Results showed that the estrogen-like treatment was acting on both immune cells of the brain as well as on oligodendrocytes, together resulting in repair of myelin and less disability.

Drug developers often optimize therapies by targeting only one single cell type. By contrast, this study confirms that this estrogen-like compound can combat MS via complementary effects on two distinct cell types. Voskuhl and other UCLA researchers are in fact now developing a next-generation estrogen-like compound with robust biochemical effects on oligodendrocytes and immune cells in the brain.

Voskuhl, who is a professor of neurology and directs UCLA's Multiple Sclerosis Program, is the study's senior author. Others include first author Roy Y. Kim, a graduate student in Voskuhl's lab; Darian Mangu, Alexandria S. Hoffman, Rojan Kovash, and Eunice Jung -- all UCLA undergraduates; and Noriko Itoh, all of the Department of Neurology at UCLA's David Geffen School of Medicine.

Funding was provided by the National Institutes of Health and by grants from the Conrad Hilton Foundation, the California Community Foundation, and the Tom Sherak MS Hope Foundation.


Story Source:

Materials provided by University of California - Los Angeles. Note: Content may be edited for style and length.


Journal Reference:

  1. Roy Y Kim, Darian Mangu, Alexandria S Hoffman, Rojan Kovash, Eunice Jung, Noriko Itoh, Rhonda Voskuhl. Oestrogen receptor β ligand acts on CD11c+ cells to mediate protection in experimental autoimmune encephalomyelitis. Brain, 2018; 141 (1): 132 DOI: 10.1093/brain/awx315

Cite This Page:

University of California - Los Angeles. "Novel complementary effects of estrogen treatment in multiple sclerosis." ScienceDaily. ScienceDaily, 28 December 2017. <www.sciencedaily.com/releases/2017/12/171228132042.htm>.
University of California - Los Angeles. (2017, December 28). Novel complementary effects of estrogen treatment in multiple sclerosis. ScienceDaily. Retrieved March 27, 2024 from www.sciencedaily.com/releases/2017/12/171228132042.htm
University of California - Los Angeles. "Novel complementary effects of estrogen treatment in multiple sclerosis." ScienceDaily. www.sciencedaily.com/releases/2017/12/171228132042.htm (accessed March 27, 2024).

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