Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the MPTP mouse model of Parkinson's disease

• Published in: Brain research Vol. 1306; pp. 176 - 183
• Main Authors: Kim, Sung Tae, Son, Hyo Jin, Choi, Ji Hyun, Ji, In Jung, Hwang, Onyou
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.01.2010; Elsevier
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Biomechanical Phenomena; Chromatography, High Pressure Liquid; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disability Evaluation; Disease Models, Animal; Dopamine; Dopamine - metabolism; Dyskinesia, Drug-Induced - diagnosis; Dyskinesia, Drug-Induced - etiology; Dyskinesia, Drug-Induced - metabolism; Forelimb; Gait; Homovanillic Acid - metabolism; Horizontal grid test; Male; Medical sciences; Mice; Mice, Inbred C57BL; Motor deficit; Motor Skills; MPTP; Neurology; Organic mental disorders. Neuropsychology; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - complications; Parkinsonian Disorders - diagnosis; Phenylacetates - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Time Factors; Vertical grid test; Motor deficit; Parkinson's disease; Dopamine; MPTP; Vertical grid test; Horizontal grid test; Animal model; Nervous system diseases; Rodentia; Parkinson disease; Instrumentation; Catecholamine; Cerebral disorder; Toxin; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Neurotoxin; Neurotransmitter; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.09.103

Abstract 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.