Original Research ARTICLE

Front. Aging Neurosci., 11 December 2009 | doi: 10.3389/neuro.24.003.2009

Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA
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.
Keywords:
age-related, chronic animal model, mitochondrial defects, neurodegeneration, Parkinson’s disease
Citation:
Patki G, Che Y and Lau Y-S (2009). Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease. Front. Ag. Neurosci. 1:3. doi: 10.3389/neuro.24.003.2009
Received:
27 October 2009;
 Paper pending published:
12 November 2009;
Accepted:
16 November 2009;
 Published online:
11 December 2009.

Edited by:

Paula I. Moreira, University of Coimbra, Portugal

Reviewed by:

Sandra M. Cardoso, University of Coimbra, Portugal
Russell H. Swerdlow, University of Kansas Medical Center, USA
Ana Navarro, University of Cadiz, Spain
Copyright:
© 2009 Patki, Che and Lau. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence:
Yuen-Sum Lau, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 521 Science and Research Building 2, Houston, TX 77204, USA. e-mail: ylau2@uh.edu
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