"I advocate the early use of pergolide (dopamine agonist) in horses that we suspect will develop the condition at a younger
age (i.e., the horse that has been chronically obese and insulin-resistant) and the provision of adequate antioxidants in
the diet — vitamin E primarily," Frank says.
What causes the dopaminergic neurons to degenerate? According to McFarlane, "Oxidative stress results in modification of cellular
components including proteins, DNA and cell-membrane lipids, because of excessive exposure to exogenous or endogenous free-radicals."
This leads to neurodegeneration. McFarlane looked at the pituitary and the hypothalamus of horses with PPID, using immunohistochemistry
to see if there was degeneration of the dopaminergic neurons and also to look for markers of oxidative stress, as a potential
mechanism of why those neurons might be damaged.
McFarlane found a marked decrease in dopaminergic neurons at the level of the pituitary and hypothalamus both at their nerve
terminals and cell bodies. Oxidative stress markers were increased, and, similar to what is observed in humans with Parkinson's
disease, there was an accumulation of the protein alpha-synuclein in horses with PPID.
A neurodegenerative disease
"In summary," McFarlane says, "PPID likely is a neurodegenerative disease, and oxidative stress and abnormal protein accumulation
is associated with the neurodegeneration of those dopaminergic neurons." This theory fits with what is known, both in how
horses with PPID respond to treatment with pergolide, a drug that replaces dopamine, and also from the older work from the
1980s showing decreased pituitary dopamine concentration," McFarlane says.
Regardless of the progress in determining the probable cause of the disease, equine practitioners don't have an early enough
diagnostic marker yet of PPID. What might be effective would be to recognize and to treat affected horses during the early
stages of the disease, before the neurons are irreparably damaged.
Researchers now are looking for improved markers of the disease that will allow veterinarians to recognize affected horses
earlier, and to see whether they can give them neuroprotective therapies, such as antioxidants, to slow or stop PPID. "(Lack
of early recognition/diagnosis) keeps us from being able to say that antioxidant supplementation will help this condition,"