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Comparing mitochondrial dysfunction in acute and chronic mouse models of Parkinson's disease
Author(s) -
Patki Gaurav,
Lau YuenSum
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1013.4
Subject(s) - mptp , oxidative stress , parkinson's disease , mitochondrion , medicine , dopaminergic , pharmacology , mitochondrial permeability transition pore , endocrinology , chemistry , dopamine , disease , apoptosis , programmed cell death , biochemistry
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of nigrostriatal dopaminergic neurons. The etiology of PD is unsolved, although many hypotheses based on genetic, environmental and cytotoxic factors have been examined. According to in vitro and acute in vivo studies, oxidative stress and mitochondrial dysfunction leading to neuronal death have been implicated. It is not known whether mitochondrial dysfunction is an immediate response to cytotoxic‐inducing agents or is a long‐term result of neuronal death. We investigated the striatal mitochondrial function in a chronic mouse model of PD in 8‐month old, male, C57/BL retired breeders treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP, 15 mg/kg) and probenecid (250 mg/kg) twice a week for 5 weeks. We compared the chronic results with that of an acute model treated with 2 doses of MPTP (15 mg/kg), 2 hours apart. Data were collected 6 weeks after the chronic model and 2 hours after the acute model treatment. In the acute model, we detected a significant inhibition of the State 3, but not the State 4 respiration in the striatal mitochondria. No changes in mitochondrial cytochrome c (cytc) and Cu/Zn superoxide dismutase (SOD) protein levels were observed. In contrast, we did not detect mitochondrial respiratory deficiency in the chronic model but the levels of cytc and SOD were significantly decreased. Our results indicate that striatal mitochondrial toxicity is different between acute and chronic models of PD. In the chronic model, there is a long‐term loss of key mitochondrial enzymes in association with neuronal loss. The remaining intact mitochondria appear to respire in a normal rate. Supported by NINDS R01‐47920.