Paraquat-induced rodent models of Parkinson's disease: A PRISMA-compliant systematic review and meta-analysis

The relationship between paraquat exposure and Parkinson's disease (PD) has been extensively studied. Numerous paraquat-induced rodent models of PD have been developed, however, substantial variability in dosing regimens and study design complicates interpretation. Improving the translational relevance of these models is critical. The aim of this systematic review and meta-analysis was to evaluate the face validity of paraquat-induced rodent models of PD. Studies which quantitatively evaluated substantia nigra pars compacta (SNpc) neuronal loss and behavioral motor deficits were included. An electronic search in three databases was performed. A systematic review and meta-analysis was performed of 54 studies (84 experimental groups). Random-effects meta-analyses of continuous data showed a significant effect of SNpc neuronal loss (SMD=3.07, 95% CI 2.48, 3.65; I²=78.1%; p < 0.0001) and motor deficit in studies using the rotarod test, open field test, rearing, and gait analysis, but not the pole test. Subgroup analyses and meta-regression for varying studying characteristics did not account for all heterogeneity. A random-effects meta-analysis of binary data for the event that a significant motor deficit was observed according to the percent SNpc neuron loss revealed a pooled odds ratio (OR=5.08, 95% CI 0.96, 26.83; I²=71.4%; p = 0.0009) and favored a motor deficit in experimental groups that had 26% or greater SNpc neuronal loss. We discuss here how varying study characteristics contribute to the heterogeneity in results across studies. Our findings support the continued use of paraquat-induced rodent models of PD as translationally relevant models, and we highlight the importance of applying appropriate study characteristics in future studies.