Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease
Open accessAbstract
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.
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The specific down-regulation of mitochondrial processes in aged striatum could help to explain previous observations demonstrating selective vulnerability to mitochondrial toxins and stresses in the striatum of old animals.
“This specific down-regulation of mitochondrial processes in aged striatum could help to explain previous observations demonstrating selective vulnerability to mitochondrial toxins and stresses in the striatum of old animals (Brouillet et al., 1993; Patki et al., 2009).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Patki et al., 2009
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Cites
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914 · see citing works
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R., Sherer, T., Mackenzie, G., Garcia-Osuna, M., Panov, A., & Greenamyre, J. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,797 · see citing works
Mitochondrial Complex I Deficiency in Parkinson's Disease
Schapira, A. H. V., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb02325.x · Cited by 2,283 · see citing works
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987 · see citing works
MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE
Schapira, A. H. V., Cooper, J. A. D., Dexter, D. T., Jenner, P. G., Clark, J. B., & MARSDEN, C. D. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92366-0 · Cited by 1,757 · see citing works
Molecular Pathways of Neurodegeneration in Parkinson's Disease
Dawson, T. M., & Dawson, V. L. (2003) · Science · doi:10.1126/science.1087753 · Cited by 1,659 · see citing works
Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1769 · Cited by 1,570 · see citing works
Blum, D. L., Torch, S., Lambeng, N., Nissou, M.-F., Benabid, A., Sadoul, R., & Verna, J. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00003-x · Cited by 1,246 · see citing works
Abnormalities of the electron transport chain in idiopathic parkinson's disease
Parker, W. D., Boyson, S. J., & Parks, J. K. (1989) · Annals of Neurology · doi:10.1002/ana.410260606 · Cited by 1,061 · see citing works
Mitochondria take center stage in aging and neurodegeneration
Beal, M. F. (2005) · Annals of Neurology · doi:10.1002/ana.20624 · Cited by 957 · see citing works
Kraytsberg, Y., Kudryavtseva, E., McKee, A. C., Geula, C., Kowall, N. W., & Khrapko, K. (2006) · Nature Genetics · doi:10.1038/ng1778 · Cited by 884 · see citing works
α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress
Hsu, L. J., Sagara, Y., Arroyo, A., Rockenstein, E. M., Sisk, A., Mallory, M. E., Wong, J., Takenouchi, T., Hashimoto, M., & Masliah, E. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64553-1 · Cited by 716 · see citing works
Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons
Ekstrand, M. I., Terzioglu, M., Galter, D., Zhu, S., Hofstetter, C., Lindqvist, E., Thams, S., Bergstrand, A., Hansson, F. S., Trifunovic, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605208103 · Cited by 605 · see citing works
Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP
Dauer, W. T., Kholodilov, N. G., Vila, M., Trillat, A., Goodchild, R. E., Larsen, K. E., Staal, R. G. W., Tieu, K., Schmitz, Y., Yuan, C. A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172514599 · Cited by 580 · see citing works
Targeting programmed cell death in neurodegenerative diseases
Vila, M., & Przedborski, S. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1100 · Cited by 545 · see citing works
Mitochondrial Disorders in the Nervous System
DiMauro, S., & Schon, E. A. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094302 · Cited by 536 · see citing works
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
Tieu, K., Perier, C., Caspersen, C., Teismann, P., Wu, D.-C., Yan, S.-D., Naini, A., Vila, M., Jackson-Lewis, V., Ramasamy, R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318797 · Cited by 497 · see citing works
Floor, E., & Wetzel, M. G. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010268.x · Cited by 452 · see citing works
Ramsay, R. R., & Singer, T. P. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)57434-8 · Cited by 415 · see citing works
Neuronal degeneration and mitochondrial dysfunction
Schon, E. A., & Manfredi, G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17741 · Cited by 393 · see citing works
Animal Models of Action Tremor
Elble, R. J. (2008) · Movement Disorders · doi:10.1002/mds.870131306 · Cited by 381 · see citing works
Human disease, free radicals, and the oxidant/antioxidant balance
McCord, J. M. (1993) · Clinical Biochemistry · doi:10.1016/0009-9120(93)90111-i · Cited by 376 · see citing works
BRAIN, SKELETAL MUSCLE AND PLATELET HOMOGENATE MITOCHONDRIAL FUNCTION IN PARKINSON'S DISEASE
MANN, V. M., COOPER, J. M., KRIGE, D., DANIEL, S. E., SCHAPIRA, A. H. V., & MARSDEN, C. D. (1992) · Brain · doi:10.1093/brain/115.2.333 · Cited by 346 · cited 1× · see citing works
“The concept of neuronal oxidative stress and mitochondrial complex-1 inhibition has also been verifi ed in the substantia nigra pars compacta from human PD (Parker Jr. et al., 1989; Schapira et al., 1990; Mann et al., 1992; Floor and Wetzel, 1998).”
Petroske, E., Meredith, G. E., Callen, S. E., Totterdell, S., & Lau, Y.-S. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00295-0 · Cited by 331 · see citing works
Neuronal degeneration and mitochondrial dysfunction
Schon, E. A., & Manfredi, G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317741 · Cited by 326 · see citing works
Song, D. D., Shults, C. W., Sisk, A., Rockenstein, E. M., & Masliah, E. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00342-x · Cited by 294 · see citing works
Environment, Mitochondria, and Parkinson's Disease
Sherer, T., Betarbet, R., & Greenamyre, J. (2002) · The Neuroscientist · doi:10.1177/1073858402008003004 · Cited by 264 · see citing works
Calabrese, V., Scapagnini, G., Giuffrida Stella, A. M., Bates, T. E., & Clark, J. B. (2001) · Neurochemical Research · doi:10.1023/a:1010955807739 · Cited by 263 · see citing works
Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity
Gash, D. M., Rutland, K., Hudson, N. L., Sullivan, P. G., Bing, G., Cass, W. A., Pandya, J. D., Liu, M., Choi, D. Y., Hunter, R. L., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21288 · Cited by 223 · see citing works
Deleterious mitochondrial DNA mutations accumulate in aging human tissues
Arnheim, N., & Cortopassi, G. A. (1992) · Mutation Research/DNAging · doi:10.1016/0921-8734(92)90020-p · Cited by 215 · see citing works
Mice lacking alpha-synuclein are resistant to mitochondrial toxins
Klivènyi, P., Siwek, D. F., Gardian, G., Yang, L., Starkov, A. A., Cléren, C., Ferrante, R. J., Kowall, N. W., Abeliovich, A., & Beal, M. F. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.018 · Cited by 213 · see citing works
Meredith, G. E., Totterdell, S., Petroske, E., Cruz, K. S., Callison, R. C., & Lau, Y.-S. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03514-x · Cited by 212 · see citing works
Ricaurte, G. A., Irwin, I., Forno, L. S., et al. (1987) · Brain Research · doi:10.1016/0006-8993(87)90120-x · Cited by 186 · see citing works
Cytochrome c, an ideal antioxidant
Pereverzev, M. O., Vygodina, T. V., Konstantinov, A. A., & Skulachev, V. P. (2003) · Biochemical Society Transactions · doi:10.1042/bst0311312 · Cited by 150 · see citing works
Mitochondrial DNA Mutations in Disease, Aging, and Neurodegeneration
Reeve, A. K., Krishnan, K. J., & Turnbull, D. M. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.016 · Cited by 146 · see citing works
Pothakos, K., Kurz, M. J., & Lau, Y.-S. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-6 · Cited by 134 · see citing works
Kang, D., & Hamasaki, N. (2005) · Current Medicinal Chemistry · doi:10.2174/0929867053363081 · Cited by 132 · see citing works
Ali, S. F., David, S. N., Newport, G. D., Cadet, J. L., & Slikker, W. (1994) · Synapse · doi:10.1002/syn.890180105 · Cited by 124 · see citing works
Gu, G., Reyes, P. F., Golden, G. T., Woltjer, R. L., Hulette, C., Montine, T. J., & Zhang, J. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.7.634 · Cited by 122 · see citing works
The Neurodegenerative Mitochondriopathies
Swerdlow, R. H. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1095 · Cited by 112 · see citing works
Neuropathology of mitochondrial diseases
Filosto, M., Tomelleri, G., Tonin, P., et al. (2007) · Bioscience Reports · doi:10.1007/s10540-007-9034-3 · Cited by 106 · see citing works
Mitochondria and aging: A role for the permeability transition?
Crompton, M. (2004) · Aging Cell · doi:10.1046/j.1474-9728.2003.00073.x · Cited by 101 · see citing works
Novikova, L., Garris, B. L., Garris, D. R., & Lau, Y.-S. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.02.007 · Cited by 95 · see citing works
Mitochondriopathy in Parkinson Disease and Amyotrophic Lateral Sclerosis
Martin, L. J. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000248541.05552.c4 · Cited by 83 · see citing works
Lau, Y., Trobough, K. L., Crampton, J. M., & Wilson, J. A. (1990) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(90)90898-v · Cited by 75 · see citing works
Bronstein, J. M., Carvey, P. M., Chen, H., Cory‐Slechta, D. A., Monte, D. A. D., Duda, J. E., English, P. B., Goldman, S. M., Grate, S. J., Hansen, J., et al. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11702 · Cited by 69 · see citing works
Barber‐Singh, J., Seo, B. B., Nakamaru‐Ogiso, E., Lau, Y., Matsuno‐Yagi, A., & Yagi, T. (2009) · Rejuvenation Research · doi:10.1089/rej.2009.0854 · Cited by 45 · see citing works
Mitochondrial Metabolism Modulation: A New Therapeutic Approach for Parkinsons Disease
Arduíno, D. M., Esteves, A. R., Oliveira, C. R., & Cardoso, S. M. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710790966687 · Cited by 44 · see citing works
Role of Mitochondrial Deterioration in Physiological and Pathological Brain Aging
Bertoni–Freddari, C., Fattoretti, P., Giorgetti, B., Solazzi, M., Balietti, M., & Meier-Ruge, W. A. (2004) · Gerontology · doi:10.1159/000076779 · Cited by 40 · see citing works
Lau, Y., Novikova, L., & Roels, C. (2005) · Neuroscience Research · doi:10.1016/j.neures.2005.04.010 · Cited by 28 · see citing works
Critical age-related loss of cofactors of neuron cytochrome C oxidase reversed by estrogen
Jones, T. T., & Brewer, G. J. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.09.011 · Cited by 25 · see citing works
Environment, Mitochondria, and Parkinson’s Disease
Sherer, T., Betarbet, R. S., & Greenamyre, J. T. (2002) · The Neuroscientist · doi:10.1177/10758402008003004 · Cited by 22 · see citing works
Progressive Neurodegeneration in the Chronic MPTP/Probenecid Model of Parkinson’s Disease
Lau, Y. (2004) · CRC Press eBooks · doi:10.1201/9780203508596.ch11 · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Przedborski S. Jackson-Lewis V. (1998). Mechanisms of MPTP toxicity. Mov. Disord. 13(Suppl. 1), 35– 38 9613716
- Wallace D. (1997). Mitochondrial DNA mutations and bioenergetic defects in aging and degenerative diseases. In The Molecular and Genetic Basis of Neurological Disease, Rosenberg R. N. Prusiner S. B. DiMauro S. Barchi R. L., eds (Boston, Butterworth-Heinemann), pp. 237– 269
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Patki, G., Solanki, N., Atrooz, F., Allam, F., & Salim, S. (2013) · Brain Research · doi:10.1016/j.brainres.2013.09.033 · Cited by 380 · see citing works
Self-citationLau, Y.-S., Patki, G., Das-Panja, K., Le, W.-D., & Ahmad, S. O. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07626.x · Cited by 275 · see citing works
Self-citationAtlas of the aging mouse brain reveals white matter as vulnerable foci
Hahn, O., Foltz, A. G., Atkins, M., Kedir, B., Moran-Losada, P., Guldner, I. H., Munson, C., Kern, F., Pálovics, R., Lu, N., et al. (2023) · Cell · doi:10.1016/j.cell.2023.07.027 · Cited by 213 · see citing works
- Authors
- Patki, G.
- Affiliations
- University of Houston (US)
- Corresponding author
- Patki, Gaurav
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2009
- Volume
- 1
- Pages
- 3-3
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC2874410
- OpenAlex
- W2042663107
- Cited by
- 20
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2017: 4 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (47920, NS47920, R01NS047920)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- mitochondrial dysfunction, Parkinson's disease, MPTP mouse model, striatum, aging, mitochondrial respiration, oxidative stress, dopamine depletion, tyrosine hydroxylase, superoxide dismutase, cytochrome c, ATP depletion, neurodegeneration
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