Unraveling the Mystery of MS in Women

Women with MS had more S1PR2 in brains

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) Why multiple sclerosis is more common in women has been a mystery. One clue may be found in the differences between the brains of men and women.

Multiple sclerosis (MS) is a disease of the brain and spinal cord that affects three to four times as many women as men.

In MS, the patient’s immune system destroys the protective coating around nerves, resulting in nerve damage that can affect walking, talking, balance and other body functions.

Using mice susceptible to MS as well as human brain tissue, a research team set out to see which genes and proteins were different in men and women with and without MS.

The research team found a protein, called S1PR2, that was more common in the brains of women and even more common in the brains of women with MS. This protein was found in higher amounts in the area of the brain MS usually affects.

"Learn about the early signs of MS."

The senior author of this study was Robyn Klein, MD, PhD, from the Departments of Internal Medicine, Pathology and Immunology and Anatomy and Neurobiology at the Washington University School of Medicine in St. Louis, Missouri.

The research team used mice and human brain tissue in their study. A strain of mice, called SJL, was used as a model for human MS. The female mice of this strain are more susceptible to developing MS.

The researchers looked at the brain tissue of these SJL mice for genes and proteins that were different between males and females.

They found that a protein, called S1PR2, on brain blood vessels was significantly more abundant in the brains of female SJL mice than male mice. More of the S1PR2 protein was found in the cerebellum than in other parts of the brain. The cerebellum is the area typically damaged in humans who have MS.

The protein was not found to be increased in the brains of female mice that were not SJL mice.

Normally, blood vessel cells create a blood-brain barrier that blocks potentially harmful substances from entering the brain. Leakage through the vessels into the brain is seen in humans with MS. It is not known if defects in this barrier can allow inflammatory cells that cause MS to get into the central nervous system.

Since S1PR2 was known to play a role in how blood vessel cells function, the researchers tested the blood-brain barrier in SJL mice. They did this by injecting dye into the mice and tracking where it went.  

The researchers found that the dye leaked through the vessels into the cerebellum of SJL mice. This leakage was significantly greater in female mice than male mice.

In SJL mice who developed MS, the blood vessels leaked more in female mice than in male mice. The leakage was much greater in female mice with active MS than in female mice whose disease was in remission (no symptoms).

The researchers looked for S1PR2 protein in the brain tissue of 20 humans with and without MS. The levels of S1PR2 were significantly increased in the brains of patients with MS compared to those without MS.

The highest levels of S1PR2 were found in the brains of women with a type of MS called relapsing-remitting MS, which is more common in women than in men and is characterized by periods of MS symptoms that are separated by periods when the disease symptoms are not obvious.

"Our data provide strong evidence that S1PR2 acts as a general regulator of [blood-brain barrier] … function and may be targeted to treat MS in certain patients," the authors wrote.

"This is an exciting first step in resolving the mystery of why MS rates are dramatically higher in women and in finding better ways to reduce the incidence of this disorder and control symptoms," Dr. Klein said.

This study was published in the May 8 issue of The Journal of Clinical Investigation.

Funding for the research was provided by the National Institutes of Health and the Multiple Sclerosis Society.

The authors declared no conflicts of interest.

Review Date: 
May 14, 2014
Last Updated:
May 15, 2014