Le Centre hospitalier universitaire de Québec
Funded by Quebec Parkinson Network
Graduate Student Award: $30,000 over two years
Effects of Gonadial Drugs as Neuroprotectors in Animal Models of Parkinson’s Disease
Typically, more men than women develop Parkinson’s disease, and the men are diagnosed at a younger age. Women who have Parkinson’s also report that their symptoms are more severe when they are menstruating, while their estrogen levels are low. These factors have led researchers, including Nadhir Litim, to wonder if estrogen might be a protective factor or a possible treatment for the disease.
Litim and his colleagues at the Centre hospitalier universitaire de Québec are investigating the effects of using synthetic estrogen drugs to slow the degeneration of dopamine-producing brain cells, while finding a way to protect healthy cells from any harm estrogen might inflict.
Because researchers are still discovering how Parkinson’s disease targets neurons and how it spreads, Litim uses an animal model exposed to a neurotoxin known as MPTP, which mimics the symptoms of Parkinson’s disease. Both Parkinson’s disease and MPTP target specific brain cells that supply dopamine, a neurotransmitter, or hormone, that plays a role in mood, reward and addiction.
So far, Litim’s research indicates that female mice exposed to MPTP show less severe symptoms than male mice, mimicking Parkinson’s disease in men and women. Previous studies have demonstrated the protective qualities of estrogen in similar cases.
Estrogen works by minimizing the negative effects of MPTP and restoring the expression of two proteins (DAT and VMAT2) that play significant roles in releasing and transporting dopamine among brain cells. Estrogen also protects the deeper tissues in the region of the brain known as the substantia nigra. But the hormone can cause serious side effects for people with Parkinson’s disease.
If Litim and his colleagues were able to deliver drugs that include synthetic estrogen directly to the malfunctioning areas of the brain that cause Parkinson’s, they could minimize those side effects and increase estrogen’s protective role.
Litim is creating a type of drug therapy, using proteins and receptors, to deliver the estrogen directly to the areas of the brain affected by Parkinson’s. “This drug also helps protect other brain cells from damage, which is known to be caused by estrogen therapies,” he says.
Being able to observe both male and female mice models of Parkinson’s disease that have been given this treatment will allow Litim and his colleagues to see just how effective estrogen therapy is, and to open a possible new avenue for future treatments for people with Parkinson’s disease.