A highly sensitive automated complex running wheel test to detect latent motor deficits in the mouse MPTP model of Parkinson's disease.

作者: David Liebetanz , Paul Christian Baier , Walter Paulus , Katrin Meuer , Mathias Bähr

DOI: 10.1016/J.EXPNEUROL.2007.01.030

关键词:

摘要: The subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) paradigm is one of the most widely used in vivo models Parkinson's disease (PD). However, particularly mouse model it has remained difficult to reliably detect behavioural correlates for PD. In present study we apply a novel murine motor test, skill sequence (MOSS) based on computerized recording voluntary running wheel activity, and found latent deficits MPTP model. Mice are first subjected 2-week training phase. animals then receive either injections according standard (30 mg/kg) or vehicle 5 consecutive days. Running performance transiently fell during injection phase but returned baseline within few were exposed complex wheels with irregularly spaced crossbars demanding high central coordination abilities. Though both groups showed clear improvement learning wheel, displayed wheels, as indicated by reduced maximum speed distance, despite unchanged motivation. Our results demonstrate MPTP-treated mice, which can be unmasked MOSS. MOSS thus capable detecting quantifying this PD sensitivity. automated full time data collection several different parameters makes also suitable test efficient screening potential therapeutic compounds

参考文章(45)
Fiona Thomson, Parkinson's Disease Neuron. ,vol. 39, pp. 889- 909 ,(2003) , 10.1016/S0896-6273(03)00568-3
Serge Przedborski, Vernice Jackson-Lewis, Ali B. Naini, Michael Jakowec, Giselle Petzinger, Reginald Miller, Muhammad Akram, The parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP): a technical review of its utility and safety Journal of Neurochemistry. ,vol. 76, pp. 1265- 1274 ,(2001) , 10.1046/J.1471-4159.2001.00183.X
Katrin Meuer, Claudia Pitzer, Peter Teismann, Carola Krüger, Bettina Göricke, Rico Laage, Paul Lingor, Kerstin Peters, Johannes C. M. Schlachetzki, Kazuto Kobayashi, Gunnar P. H. Dietz, Daniela Weber, Boris Ferger, Wolf-Rüdiger Schäbitz, Alfred Bach, Jörg B. Schulz, Mathias Bähr, Armin Schneider, Jochen H. Weishaupt, Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. Journal of Neurochemistry. ,vol. 97, pp. 675- 686 ,(2006) , 10.1111/J.1471-4159.2006.03727.X
Darren C. Robertson, Oliver Schmidt, Natalia Ninkina, Paul A. Jones, John Sharkey, Vladimir L. Buchman, Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ-synuclein, α-synuclein and double α/γ-synuclein null mutant mice Journal of Neurochemistry. ,vol. 89, pp. 1126- 1136 ,(2004) , 10.1111/J.1471-4159.2004.02378.X
Jennifer L Tillerson, W Michael Caudle, Maria E Reverón, Gary W Miller, None, Detection of behavioral impairments correlated to neurochemical deficits in mice treated with moderate doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Experimental Neurology. ,vol. 178, pp. 80- 90 ,(2002) , 10.1006/EXNR.2002.8021
Richard E. Heikkila, Patricia K. Sonsalla, The MPTP-treated mouse as a model of Parkinsonism: How good is it? Neurochemistry International. ,vol. 20, pp. 299- 303 ,(1992) , 10.1016/0197-0186(92)90256-Q
Dong-Youn Hwang, Sheila M Fleming, Paul Ardayfio, Taylor Moran-Gates, Hansoo Kim, Frank I Tarazi, Marie-Francoise Chesselet, Kwang-Soo Kim, 3,4-Dihydroxyphenylalanine Reverses the Motor Deficits in Pitx3-Deficient Aphakia Mice: Behavioral Characterization of a Novel Genetic Model of Parkinson's Disease The Journal of Neuroscience. ,vol. 25, pp. 2132- 2137 ,(2005) , 10.1523/JNEUROSCI.3718-04.2005
Brian D. West, Paul J. Shughrue, Amy E.H. Vanko, Richard W. Ransom, Gene G. Kinney, Amphetamine-induced locomotor activity is reduced in mice following MPTP treatment but not following selegiline/MPTP treatment. Pharmacology, Biochemistry and Behavior. ,vol. 84, pp. 158- 161 ,(2006) , 10.1016/J.PBB.2006.04.022
H. Bernheimer, W. Birkmayer, O. Hornykiewicz, K. Jellinger, F. Seitelberger, Brain dopamine and the syndromes of Parkinson and Huntington Clinical, morphological and neurochemical correlations Journal of the Neurological Sciences. ,vol. 20, pp. 415- 455 ,(1973) , 10.1016/0022-510X(73)90175-5