Behavioral phenotyping of the MPTP mouse model of Parkinson's disease

Abstract

In mice, the systemical or intracranial application of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to severe damage to the nigrostriatal dopaminergic system. This can result in a variety of symptoms concerning motor control resembling those in human Parkinson's disease, such as akinesia, rigidity, tremor, gait and posture disturbances. The aim of this work is to review a variety of behavioral paradigms for these and other symptoms, which have been used to characterize behavioral changes in mice after MPTP treatment. Main results are summarized, and general influential factors as well as potential problems in the experimental procedures are discussed, which should be taken into account when conducting behavioral analyses in mice with parkinsonian symptoms. Since there is reliable evidence (e.g. from strain comparisons) that the susceptibility of the nigrostriatal pathway to neurodegeneration is probably genetically influenced, relevant genes can be expected to be identified in the future. Therefore, the points discussed here will be useful not only for further applications in the MPTP mouse model, but also more generally for the behavioral characterization of future mouse models of PD, e.g. mice with a manipulation of genes relevant to the function of the basal ganglia.