Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the MPTP mouse model of Parkinson's disease.
Parkinson's disease (PD) is caused by selective degeneration of the nigral dopaminergic (DArgic) neurons and is accompanied by motor dysfunctions such as tremor, akinesia, and rigidity. Changes in the degree of motor deficit can be utilized as a noninvasive way of assessing alterations in the number of DArgic neurons and/or the amount of DA in animal models of PD, such as mice systemically administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, in order to develop sensitive methods to detect DA-associated motor deficits, we designed a new test called vertical grid test and modified the existing horizontal grid test. After acute MPTP treatment, decreases in the levels of striatal DA (17.4% of control), dihydroxyphenylacetic acid (33.3%), and homovanillic acid (40.5%) were observed. On the modified horizontal grid test, the MPTP-administered mice exhibited average forelimb step distance that was lower than control (82.58%) and correlated with the striatal DA levels. On the vertical grid test, the MPTP-treated mice took dramatically longer total time to climb down (220.94%) and time to make the turn (339.29%) compared to control, and this correlated well with the degree of striatal DA depletion. In comparison, the gait test produced only a small, albeit statistically significant, reduction in the mean stride length (94.55% of control). These results show that the vertical grid test can provide a sensitive measure of motor deficit in mice following administration of MPTP.
Kim
Sung Tae
ST
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Son
Hyo Jin
HJ
Choi
Ji Hyun
JH
Ji
In Jung
IJ
Hwang
Onyou
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001696:Biomechanical Phenomena; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004185:Disability Evaluation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D005552:Forelimb; D005684:Gait; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009048:Motor Skills; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis*; D010648:Phenylacetates / Q000378:metabolism; D013997:Time Factors
D010648:Phenylacetates; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid