Understanding Neurodegenerative Disease

As the concept of “one health, one medicine” continues to grow, Dr. Dianne McFarlane, OSU assistant professor of physiological sciences, uses a horse model as she investigates the pathogenesis of neurodegeneration.

McFarlane strives to better understand the biological changes that accompany aging and the age-related factors that promote risk of neurodegenerative disease.

“If we can understand what causes the degeneration in horses, by extension we can hopefully determine what is going on with other degenerative diseases in people like Parkinson’s, Huntington’s and Alzheimer’s,” she says.

“It is well known that the number-one risk factor for this condition is age. What is not well understood is exactly how age predisposes to neurodegeneration. Is it due to a lifetime accumulation of damaged cells or cellular components, a failure of some critical cellular function, or the depletion of a limited body resource?

“If we understood how age contributes to the risk of neurodegeneration, we would have an opportunity to develop strategies to prevent or delay onset of these devastating diseases.”

McFarlane, whose research goals include developing better tests and implementing preventative strategies than can ultimately be transferred to humans, recently completed the third year on a five-year National Institutes of Health grant.

Her research project, “Initiating Factors of Neurodengeration,” focuses on what causes the neurons to degenerate. Neurons are sensitive to a number of injuries, and similar processes seem to underlie neurodegeneration in many diseases.

Accumulation of nonfunctional, misfolded proteins, accumulation of damaged organelles, injury from oxidative stress or inflammation are all considered likely contributors to the neurodegenerative process in Parkinson’s disease, Alzheimer’s disease, ALS and Huntington’s disease.

McFarlane grapples with what initiates these injuries and what makes certain individuals more susceptible than others to develop the disease.

“Currently, we are characterizing the type of changes that occur in the dopamine producing neurons in equine pituitary pars intermedia dysfunction (a neurodegenerative disease of old horses referred to as PPID) to see just how similar those neuron injuries are to those that occur with Parkinson’s disease,” she says.

Dopamine is an important chemical in regulating the horse’s production of hormones from the pituitary gland, says McFarlane, who has been studying PPID for more than 10 years.

But horses with PPID lack available dopamine, and as a consequence, hormone production from the intermediate lobe of the pituitary goes unchecked, resulting in very high blood concentrations of hormones. This, in turn, leads to the wide array of clinical signs in horses with PPID, McFarlane says.

“The same types of neurons degenerate in humans with Parkinson’s disease. However they are located in a different part of the brain, a region that regulates movement. Consequently, people with Parkinson’s disease have motor disorders such as muscle tremors and difficulty initiating movement. So while the diseases don’t look alike, the primary cause or causes of the disease may be very similar.”

Why study old horses? To McFarlane’s knowledge, PPID is the only naturally occurring degenerative disease of dopamine-producing neurons, other than Parkinson’s disease.

“Aging horses give us a naturally occurring model in which to study this condition. It has the advantage over an experiment-induced model of allowing us to investigate firsthand how the body and systems within it change during aging and disease development.

“Classically, experimental models for studying neurodegeneration involve administering high doses of chemicals or drugs that are toxic to the specific neurons of interest. We have learned a lot from these models, but clearly the vast majority of people and animals that spontaneously develop neurodegenerative disease are not exposed to high doses of these unusual drugs or chemicals,” she says.

“A naturally occurring disease model lets us ask such questions as ‘What causes the disease,’ and ‘Why did this animal or person develop the disease, while another did not?’”

Another advantage to the horse model is that PPID is very common among aged horses. About 15 to 20 percent of all horses will develop this disease, whereas in humans, Parkinson’s disease is relatively rare. Only 1 to 3 percent of seniors will develop Parkinson’s disease. The high prevalence of PPID facilitates population-based studies.

There has long been a concern that environmental factors, such as exposure to agricultural chemicals or heavy metals, may increase the risk of Parkinson’s disease. “Studying the relationship of agricultural chemicals, neurodegeneration and PPID may help answer this question,” McFarlane says.

“We hope to gain valuable insights to improve quality of life for humans and animals. It’s well worth the investment when the end result can benefit so many.”

“IF WE UNDERSTOOD HOW AGE CONTRIBUTES TO THE RISK OF NEURODEGENERATION, WE WOULD HAVE AN OPPORTUNITY TO DEVELOP STRATEGIES TO PREVENT OR DELAY ONSET OF THESE DEVASTATING DISEASES.”

— DR. DIANNE MCFARLANE

“This year, students will perform more than 4,000 surgical procedures and numerous other clinical procedures …. There will be more novel educational approaches to improve student hands-on