Chronic L-DOPA induces hyperactivity, normalization of gait and dyskinetic behavior in MitoPark mice

Genes, Brain, and Behavior
S GellhaarDagmar Galter

Abstract

Dopamine (DA) replacement therapy continues to be the gold standard treatment for Parkinson's disease (PD), as it improves key motor symptoms including bradykinesia and gait disturbances. With time, treatment induces side effects in the majority of patients, known as L-DOPA-induced dyskinesia (LID), which are often studied in animals by the use of unilateral, toxin-induced rodent models. In this study, we used the progressive, genetic PD model MitoPark to specifically evaluate bilateral changes in motor behavior following long-term L-DOPA treatment at three different stages of striatal DA depletion. Besides locomotor activity, we assessed changes in gait with two automated gait analysis systems and the development of dyskinetic behavior. Long-term treatment with a moderate, clinically relevant dose of L-DOPA (8 mg/kg) gradually produced age-dependent hyperactivity in MitoPark mice. In voluntary and forced gait analyses, we show that MitoPark mice with severe DA depletion have distinct gait characteristics, which are normalized to control levels following long-term L-DOPA treatment. The cylinder test showed an age-dependent and gradual development of bilateral LID. Significant increase in striatal FosB and prodynorphin expressio...Continue Reading

References

May 1, 1991·Journal of the Neurological Sciences·O BlinG Serratrice
Feb 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dong-Youn HwangKwang-Soo Kim
Jul 27, 2005·Journal of Neuroengineering and Rehabilitation·Ivo AmendeThomas G Hampton
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mats I EkstrandNils-Göran Larsson
Feb 19, 2008·The FEBS Journal·Mügen Terzioglu, Dagmar Galter
Sep 16, 2008·Molecular and Cellular Neurosciences·Marie WesterlundDagmar Galter
Oct 5, 2010·Progress in Brain Research·Susan H Fox, Jonathan M Brotchie
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yunmin DingUn Jung Kang
Oct 20, 2011·Behavioural Brain Research·J E WestinY Temel
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Jan 31, 2013·Experimental Neurology·Nicolas MorinThérèse Di Paolo
Oct 22, 2013·Neurobiology of Disease·Ramiro González-Aparicio, Rosario Moratalla

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Citations

Sep 5, 2015·International Journal of Molecular Sciences·Yu LuoXin Qi
Sep 13, 2015·Behavioural Brain Research·Ria de HaasJan A Smeitink
Jun 19, 2015·Brain Research·Lufei ShanCristina M Bäckman
Jan 11, 2017·Cephalalgia : an International Journal of Headache·Thomas List, Rigmor Højland Jensen

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Methods Mentioned

BETA
transgenic

Software Mentioned

catwalk
MitoPark
image j
axiovision
Prism
jwatcher

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