%A Patki,Gaurav %A Che,Yi %A Lau,Yuen-Sum %D 2009 %J Frontiers in Aging Neuroscience %C %F %G English %K age-related,chronic animal model,mitochondrial defects,neurodegeneration,Parkinson's disease %Q %R 10.3389/neuro.24.003.2009 %W %L %M %P %7 %8 2009-December-11 %9 Original Research %+ Prof Yuen-Sum Lau,University of Houston,Department of Pharmacological and Pharmaceutical Sciences,Houston,United States,ylau2@uh.edu %# %! Mitochondrial Dysfunction in Chronic Parkinsonism %* %< %T Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease %U https://www.frontiersin.org/articles/10.3389/neuro.24.003.2009 %V 1 %0 JOURNAL ARTICLE %@ 1663-4365 %X Mitochondrial oxidative stress and dysfunction has been implicated as a possible mechanism for the onset and progression of Parkinson-like neurodegeneration. However, long-term mitochondrial defects in chronic animal neurodegenerative models have not been demonstrated. In this study, we investigated the function of striatal mitochondria 6 weeks after the induction of a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (MPD). Although severe depression of mitochondrial respiration was observed immediately after acute administrations of MPTP, we failed to detect a significant mitochondrial inhibition in presence of striatal dopamine (DA) deficit 6 weeks after the chronic MPD induction in young adult mice. In contrast, when aged mice were chronically treated with MPTP and at 6 weeks post-treatment, these animals suffered an inhibition of the basal (state 4) and adenosine 5′-diphosphate-stimulated (state 3) respiration and a fall in adenosine triphosphate level in the striatal mitochondria. The aged chronic MPD also brought about a sustained diminution of striatal anti-oxidant enzyme levels including that of superoxide dismutases and cytochrome c. The mitochondrial deficits in the striatum of aged chronic MPD 6 weeks after treatment were further correlated with significant losses of striatal DA, tyrosine hydroxylase, DA uptake transporter, and with impaired movement when tested on a challenging beam. Our findings suggest that MPTP may trigger the neurodegenerative process by obstructing the mitochondrial function; however, striatal mitochondria in young animals may potentially rejuvenate, whereas mitochondrial dysfunction is sustained in the aged chronic MPD. Therefore, the aged chronic MPD may serve as a suitable investigative model for further elucidating the integral relationship between mitochondrial dysfunction and neurodegenerative disorder, and for assessing the therapeutic efficacy of mitochondrial protective agents as potential neuroprotective drugs.