Automated gait analysis in bilateral parkinsonian rats and the role of L-DOPA therapy.
Gait disturbances and postural instability represent major sources of morbidity in Parkinson's disease (PD), and respond poorly to current treatment options. Some aspects of gait disturbances can be observed in rodent models of PD; however, knowledge regarding the stability of rodent gait patterns over time is lacking. Here we investigated the temporal constancy and reproducibility of gait patterns in neurologically intact and bilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, by using an automated quantitative gait analysis method (CatWalk). The bilateral neurotoxin injections into the medial forebrain bundle resulted in an average dopamine (DA) loss of 70% in each striata, which corresponds to the DA levels observed in moderate-mid stage human PD. Rats were tested weekly during one month, and we found that in intact rats all parameters investigated remained constant over multiple tests. The 6-OHDA lesioned rats were impaired in several aspects of gait, such as stride length, swing speed, stance duration, step cycle duration, and base of support. However the stance and step cycle deficits were transient, the performance of 6-OHDA lesioned rats were indistinguishable from control rats by the last test session with regard to these parameters. Finally, we found that administration of a single dose of levodopa (L-DOPA) to the 6-OHDA lesioned rats could counteract all but one observed deficits. Based on these findings we conclude that the gait pattern of intact rats is highly reproducible, 6-OHDA lesioned rats display impairments in gait, and L-DOPA can counteract most deficits seen in this model of experimental PD.
Department of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, 2500 Copenhagen-Valby, Denmark. JEWE@Lundbeck.com
J E
JE
Westin
M L F
ML
Janssen
T N
TN
Sager
Y
Y
Temel
D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005684:Gait / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine