Parkinson’s Disease: Sudden Drop in Testosterone may Trigger Symptoms

 Kalipada Pahan, Ph.D. The Floyd A. Davis, M.D., Endowed Chair of Neurology Professor Departments of Neurological Sciences, Biochemistry and Pharmacology Rush University Medical Center 1735 West Harrison St, Suite 320 Chicago, IL 60612 MedicalResearch.com Interview with: Kalipada Pahan, Ph.D.

The Floyd A. Davis, M.D., Endowed Chair of Neurology
Professor
Departments of Neurological Sciences, Biochemistry and Pharmacology
Rush University Medical Center
1735 West Harrison St, Suite 320 Chicago, IL 60612

MedicalResearch.com: What are the main findings of the study?

Dr. Pahan: While different toxins and a number of complex genetic approaches are used to model Parkinson’s disease in mice, this study delineates that simple castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice. This simple, but persistent, model may be helpful in discovering drugs against Parkinson’s disease. Furthermore, these results suggest that sudden drop of testosterone level could trigger Parkinson’s disease.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Pahan: Different toxins failed to induce a persistent and stable model for Parkinson’s disease. Therefore, in the first place, it was little bit surprising for us that it could be possible by simple castration. However, the discovery of underlying mechanisms has helped us to understand the phenomenon and made this study very exciting. Interestingly, castration does not cause Parkinson’s like symptoms in male mice deficient in inducible nitric oxide gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Pahan: Preservation of testosterone in males may be an important step to become resistant to Parkinson’s disease.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Pahan: Future research must be conducted to see how we could potentially target testosterone levels in human males in order to find a viable treatment for Parkinson’s disease.

Citation:

Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase

Khasnavis S, Ghosh A, Roy A, Pahan K.
J Biol Chem. 2013 Jul 19;288(29):20843-55. doi: 10.1074/jbc.M112.443556.
Epub 2013 Jun 6.

Press Release:Sudden Decline in Testosterone May Cause Parkinson’s Disease Symptoms in Men
(CHICAGO) – The results of a new study by neurological researchers at Rush University Medical Center show that a sudden decrease of testosterone, the male sex hormone, may cause Parkinson’s like symptoms in male mice. The findings were recently published in the Journal of Biological Chemistry.One of the major roadblocks for discovering drugs against Parkinson’s disease is the unavailability of a reliable animal model for this disease.“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 male mice,” said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush. “We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson’s pathology in male mice.”

“In men, testosterone levels are intimately coupled to many disease processes,” said Pahan. Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year. However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson’s disease.

“Therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson’s disease,” said Pahan.

Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson’s disease. Nitric oxide is an important molecule for our brain and the body.

“However, when nitric oxide is produced within the brain in excess by a protein called inducible nitric oxide synthase, neurons start dying,” said Pahan.

“This study has become more fascinating than we thought,” said Pahan. “After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically. Interestingly, castration does not cause Parkinson’s like symptoms in male mice deficient in iNOS gene, 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,” said Pahan.

Other researchers at Rush involved in this study were Saurabh Khasnavis, PhD, student, Anamitra Ghosh, PhD, student, and Avik Roy, PhD, research assistant professor.

This research was supported by a grant from the National Institutes of Health that received the highest score for its scientific merit in the particular cycle it was reviewed.

Parkinson’s is a slowly progressive disease that affects a small area of cells within the mid-brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical neurotransmitter, dopamine. The decrease in dopamine results in one or more of the classic signs of Parkinson’s disease that includes resting tremor on one side of the body; generalized slowness of movement; stiffness of limbs and gait or balance problems. The cause of the disease is unknown. Both environmental and genetic causes of the disease have been postulated.

Parkinson’s disease affects about 1.2 million patients in the United States and Canada. Although 15 percent of patients are diagnosed before age 50, it is generally considered a disease that targets older adults, affecting one of every 100 persons over the age of 60. This disease appears to be slightly more common in men than women.