Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease
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...
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doaj-85e6cf2ce9484131abf5043e003ef5aa2020-11-25T00:01:33ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652009-12-01110.3389/neuro.24.003.20091148Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's diseaseGaurav Patki0Yi Che1Yuen-Sum Lau2University of HoustonUniversity of HoustonUniversity of HoustonMitochondrial 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 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 ADP-stimulated (state 3) respiration and a fall in ATP 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 dopamine, tyrosine hydroxylase, dopamine 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 drugshttp://journal.frontiersin.org/Journal/10.3389/neuro.24.003.2009/fullParkinson's diseaseneurodegenerationage-relatedchronic animal modelmitochondrial defects |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gaurav Patki Yi Che Yuen-Sum Lau |
spellingShingle |
Gaurav Patki Yi Che Yuen-Sum Lau Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease Frontiers in Aging Neuroscience Parkinson's disease neurodegeneration age-related chronic animal model mitochondrial defects |
author_facet |
Gaurav Patki Yi Che Yuen-Sum Lau |
author_sort |
Gaurav Patki |
title |
Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease |
title_short |
Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease |
title_full |
Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease |
title_fullStr |
Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease |
title_full_unstemmed |
Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease |
title_sort |
mitochondrial dysfunction in the striatum of aged chronic mouse model of parkinson's disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2009-12-01 |
description |
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 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 ADP-stimulated (state 3) respiration and a fall in ATP 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 dopamine, tyrosine hydroxylase, dopamine 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 |
topic |
Parkinson's disease neurodegeneration age-related chronic animal model mitochondrial defects |
url |
http://journal.frontiersin.org/Journal/10.3389/neuro.24.003.2009/full |
work_keys_str_mv |
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