In what could give hope to the 2.5 million sufferers of multiple sclerosis (MS) worldwide, a new study reports that the hormone prolactin, the levels of which spike during pregnancy, mended nerve damage in mice.
MS is a chronic degenerative disease that causes inflammation of the central nervous system. The onset of this disorder, which strikes women twice as frequently as men, is typically between the ages of 20 and 40 and is characterized by a multitude of symptoms ranging from muscle fatigue and short-term memory loss to complete loss of motility in severe cases. The illness is believed to result from impaired signaling between neurons in the brain caused by a reduction in myelin. This fatty material is an insulator covering and modulating a part of the nerve cell called the axon, which transmits electrical signals to other cells. The immune system in MS patients is known to disrupt myelin formation in axons and in the brain's white matter.
Symptoms of multiple sclerosis (MS) are known to abate during pregnancy, a phenomenon first documented by French scientists in 1998. Christian Confavreux, a neurologist at Pierre Wertheimer Neurological Hospital in Lyon, France, and a member of that team, says that pregnancy is more effective at keeping MS in check than drugs commonly used to treat it. "These observations imply looking for the immunological changes and also the hormonal changes pertaining to pregnancy," he says, "at the background of the beneficial effect."
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Toward that end, scientists at the University of Calgary in Canada, devised several mouse models to help determine whether pregnancy affects myelin production.
"It was thought that during pregnancy, their immune systems no longer destroyed the myelin," says Samuel Weiss of Hotchkiss Brain Institute in Calgary and co-author of the study published in The Journal of Neuroscience. "No previous study has tested whether pregnancy actually results in the production of new myelin, which may explain [the] improvement of symptoms."
Weiss and his colleagues compared healthy pregnant and virgin mice of the same age to determine whether differences in myelin formation were taking place. The researchers found that there were twice as many oligodendrocytes (nerve cells that produce myelin) in the brains of pregnant mice and, also, that the mice continued to produce oligodendrocytes throughout their pregnancies, leading to 50 percent more myelin sheathing in their nerve cells than in those of their virgin counterparts.
The research team then injected both sets of mice with a detergent that caused the demyelination of their nerve cells. Two weeks later, the pregnant mice had doubled their output of myelin.
The scientists discovered that if they injected pregnant mice with prolactin, the healthy animals produced more myelin and the demyelinated mice formed new myelin. The reason, say researchers: the hormone stimulates production of more oligodendrocyte stem cells, leading to more oligodendrocytes and therefore more myelin. The authors state that myelin formation was also improved in male mice, which showed an increase in prolactin levels.
"This study provides compelling evidence that the maternal brain is dynamic and provides meaningful clues about the mechanisms of neuronal plasticity," says Kelly Lambert, chair of the psychology department of Randolph-Macon College in Ashland, Va. "Learning more about how the brain changes to adapt to increased environmental demands will lead to an enhanced understanding of many clinical conditions haunting the human nervous system today—MS, learning disabilities, Alzheimer's disease—as well as provide clues about experiencing a more seamless aging process."
The Calgary group is planning to do more animal testing to determine prolactin's effectiveness in treating MS. Weiss says that if all goes well, the hormone could then move on to human testing. Confavreux says that patients in France and Italy are currently being enrolled in an MS treatment study using progesterone, another of the hormones that surge during pregnancy.
