Science/Tech

Mouse Study Shows Link Between Low Testosterone and Parkinson's Disease

Mouse Study Shows Link Between Low Testosterone and Parkinson's Disease
The sudden decline in low testosterone caused nitric oxide levels spike, killing the brain's neurons. Creative Commons

Scientists are struggling to find a cure for Parkinson's disease. The search has yielded a number of therapies, including deep brain stimulation, but many possible treatments can only work for so long. What makes a cure even more elusive is the scarcity of animal models for testing treatments. But even with these hurdles, a group of researchers found that certain symptoms of Parkinson's start to appear when mice suddenly lose their testosterone.

"While scientists use different toxins and a number of complex genetic approaches to model Parkinson's disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson's-like pathology and symptoms in mice," Dr. Kalipada Pahan, lead author of the study and professor of neurological sciences and biochemistry at Rush University Medical Center, said in a statement.

Testosterone levels typically decline by one percent for every year after a male reaches their prime in their mid-30s, Pahan said, however, outside stimulus, such as stress or other life events could increase the speed of decline, possibly increasing that person's chances of developing Parkinson's.

Parkinson's disease is a neurodegenerative disease. Someone with the disease progressively loses control of his or her central nervous system. While hand tremors are among the most common symptoms, other symptoms can include an inability to show expression, soft or slurred speech, and muscle stiffness. An estimated 500,000 people in the U.S. have the disease, according to the National Institutes of Health, but other estimates are much higher. Studies have also shown that men are 1.5 times more likely to have the disease than women. Because of this, the connection between testosterone and Parkinson's may be plausible.

With the mice, Pahan found that after castration, a protein known as inducible nitric oxide synthase (iNOS) produced higher levels of the signaling molecule nitric oxide. When this happened, it caused the brain's neurons to die, and Parkinson's-like symptoms to develop. Castrated mice that had the genetic absence of the iNOS gene, however, didn't show any symptoms of Parkinson's, "indicating that loss of testosterone causes symptoms via increased nitric oxide production."

"Further research must be conducted to see how we could potentially target testosterone levels in human males in order to find a viable treatment," Pahan writes.

Low testosterone levels have also been linked to Alzheimer's disease, another neurodegenerative disease. Specifically, researchers found that low circulating blood levels of testosterone were associated with Alzheimer's disease, years before a patient was even diagnosed.

"It is quite possible that circulating free testosterone has a broad range of influences on the aging brain," Dr. Susan Resnick, an investigator in the National Institute of Aging's Laboratoy of Personality and Cognition, said . "The effects of some of these influences — such as the role of testosterone in the development of certain types of memory loss and AD — are just beginning to be explored."

 

Source: Khasnavis S, Ghosh A, Roy A, et al. Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase. The Journal of Biochemistry. 2013.

Wooten G, Currie L, Bovbjerg V, et al. Are men at greater risk for Parkinson's disease than women? The Journal of Neurology, Neurosurgery, and Psychiatry. 2013.

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