Sensorimotor assessment of the unilateral 6-hydroxydopamine mouse model of Parkinson's disease

Abstract

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by marked impairments in motor function caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Animal models of PD have traditionally been based on toxins, such as 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), that selectively lesion dopaminergic neurons. Motor impairments from 6-OHDA lesions of SNc neurons are well characterized in rats, but much less work has been done in mice. In this study, we compare the effectiveness of a series of drug-free behavioral tests in assessing sensorimotor impairments in the unilateral 6-OHDA mouse model, including six tests used for the first time in this PD mouse model (the automated treadmill “DigiGait” test, the challenging beam test, the adhesive removal test, the pole test, the adjusting steps test, and the test of spontaneous activity) and two tests used previously in 6-OHDA-lesioned mice (the limb-use asymmetry “cylinder” test and the manual gait test). We demonstrate that the limb-use asymmetry, challenging beam, pole, adjusting steps, and spontaneous activity tests are all highly robust assays for detecting sensorimotor impairments in the 6-OHDA mouse model. We also discuss the use of the behavioral tests for specific experimental objectives, such as simple screening for well-lesioned mice in studies of PD cellular pathophysiology or comprehensive behavioral analysis in preclinical therapeutic testing using a battery of sensorimotor tests.

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

“…The adhesive label is placed on each forepaw using a forcep and the time to remove the label is recorded. We found that 6-hyrdoxydopamine-treated mice will remove the label from the unaffected limb prior to removing the label on the affected limb 19 . This test battery is easy to implement in aging studies using chronic treatments but it is also easy to use in pharmacological studies.…”

“…We have found alterations in sensorimotor function using these tests in multiple genetic and toxin mouse models of Parkinson's disease including parkin knockout, parkin Q311X, Pitx3-aphakia, alpha-synuclein overexpressing, and unilateral 6-hydroxydopamine mice 14,[16][17][18][19] . Here we show data collected from mice overexpressing human wildtype alpha-synuclein under the Thy1 promoter (Thy1-aSyn) and Pitx3-aphakia mice 18,20 .…”

“…The challenging beam test is not only useful at detecting motor performance and coordination deficits in genetic mouse models of PD but is also useful in uncovering impairments in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and 6-hydroxydopamine-treated mice and norepinephrine deficient mice 19,[23][24][25] . In addition, we find the challenging beam to be less influenced by body weight compared to other tests of motor performance and coordination (rotarod and pole test).…”

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

“…Gait analysis was done manually by measuring stride length (Glajch et al, 2012). Bottom of the fore limbs of rats were painted with kids paint and then they were allowed to walk on horizontal passage directed towards their cage.…”

Early use of oleanolic acid provides protection against 6-hydroxydopamine induced dopamine neurodegeneration

“…The use of either the left, right or both forelimbs for initial contact with the wall or floor of the cylinder was recorded. The percentage use of the limb contralateral to the lesion (contra) was expressed as a percentage of the contralateral limb on the total number of touches on the cylinder wall (Glajch et al, 2012).…”