Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease

Parkinsonʹs disease (PD) is a leading cause of neurologic disability in the aged population. Remarkable progress has been made in the past decade to understand the cellular and molecular events that occur in PD. However attempts to unravel the early, initiating factors in the pathogenesis of dopaminergic neurodegeneration and PD have been limited by the lack of a suitable animal model. Models in which there has been genetic or environmental manipulation are not of use in determining the natural cause of a disease. While a large scale prospective human study would be ideal, the relatively low prevalence of PD makes this approach economically and logistically infeasible. Equine pituitary pars intermedia dysfunction (PPID) is a spontaneous, progressive neuroendocrine disease that commonly affects aged horses and ponies. PPID results from neurodegeneration of the dopaminergic periventricular neurons that innervate the intermediate lobe of the pituitary. PPID is 10–20 times more prevalent than PD and may be readily diagnosed without a need for advanced imaging technology. Although the diseases are anatomically distinct, recent evidence suggests the pathogenesis of dopaminergic neuronal damage in PPID may have significant similarities to that of PD. In this review, the similarities and differences in the pathology of neurodegeneration in PPID and PD are compared. The potential utility of the horse as a model of spontaneous dopaminergic neurodegeneration is discussed.