Classic and new animal models of Parkinson's disease

Abstract

Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson's Disease (PD) is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydropiridine (MPTP), rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

Figure 1

Photomicrograph of a 6-OHDA lesioned rat striatum immunostained for tyrosine hydroxylase (TH). Densities of TH-immunoreactivity striatal fibers are clearly reduced after the 6-OHDA injection (right side) as compared to the densities of striatal TH-immunoreactivity fibers in control rat (left side).

Figure 2

Photomicrographs of nonhuman primate immunostained for tyrosine hydroxylase (TH). Dopaminergic neurons located in the substantia nigra compacta (SNc) project to the caudate (CD) and putamen (PUT). Note the markedly reduced TH immunoreactivity in the substantia nigra and striatum (CD and PUT) in the MPTP-treated monkey (b) compared to control (a).