Nonhuman primate models of Parkinson's disease (PD) have been invaluable to our understanding of the human disease and in the advancement of novel therapies for its treatment. In this review, we attempt to give a brief overview of the animal models of PD currently used, with a more comprehensive focus on the advantages and disadvantages presented by their use in the nonhuman primate. In particular, discussion addresses the 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydopyridine (MPTP), rotenone, paraquat, and maneb parkinsonian models. Additionally, the role of primate PD models in the development of novel therapies, such as trophic factor delivery, grafting, and deep brain stimulation, are described. Finally, the contribution of primate PD models to our understanding of the etiology and pathology of human PD is discussed.Key words: Parkinson's disease; Nonhuman primates; Animal models; Therapeutics
PARKINSON'S DISEASEsymptoms have taken a backseat to the motor problems that most often define PD. Although the etiology of PD Societal Impact and Biological Features remains unclear, degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) has It has been estimated that over 1 million Americans are currently living with Parkinson' disease (PD) with been recognized as a primary pathology (82). Loss of DA neurons in the SN results in increased inhibition of an additional 40,000 persons in the US diagnosed each year, producing an estimated annual cost of greater than excitatory output from the thalamus to the motor cortex, causing a generalized inhibition of both movement initi-$5.6 billion (88). While PD is often considered a disease of the elderly and age is clearly the most powerful risk ation and execution. Histology of nigral tissue from PD patients shows decreased numbers of DA neurons and factor, many patients have an early onset. In this regard, it is significant that approximately 15% of patients are the presence of Lewy bodies, intracellular inclusions, in remaining neurons. Degeneration of SNpc is associated diagnosed before the age of 50 (88).In its classical description, PD is a neurodegenerative with aberrant neuronal plasticity and molecular signaling within the basal ganglia, resulting in a chronic imdisorder affecting primarily movement, muscle control, and balance. Diagnostic hallmarks of PD include cogbalance of insufficient DA levels, aggravated by unregulated cholinergic and glutamatergic signaling (82). wheel rigidity, resting tremor, bradykinesia, masked faces, stooped posture, and shuffling gait (88). NonmoPatients are typically asymptomatic until greater than 60% of the DA cell number is lost from the substantia tor symptoms such as dementia, depression, constipation, pain, and sleep disturbances are serious unmet nigra (88). Therefore, a critical component in effectively treating the nigrostriatal pathology in PD will necessitate needs of PD patients. Scientifically, these nonmotor