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01.10.2014 | Neurology and Preclinical Neurological Studies - Original Article

6-Hydroxydopamine impairs mitochondrial function in the rat model of Parkinson’s disease: respirometric, histological, and behavioral analyses

verfasst von: Andreas Kupsch, Werner Schmidt, Zemfira Gizatullina, Grazyna Debska-Vielhaber, Jürgen Voges, Frank Striggow, Patricia Panther, Herbert Schwegler, Hans-Jochen Heinze, Stefan Vielhaber, Frank Norbert Gellerich

Erschienen in: Journal of Neural Transmission | Ausgabe 10/2014

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Abstract

Mitochondrial defects have been shown to be associated with the pathogenesis of Parkinson’s disease (PD). Yet, experience in PD research linking mitochondrial dysfunction, e.g., deregulation of oxidative phosphorylation, with neuronal degeneration and behavioral changes is rather limited. Using the 6-hydroxydopamine (6-OHDA) rat model of PD, we have investigated the potential role of mitochondria in dopaminergic neuronal cell death in the substantia nigra pars compacta by high-resolution respirometry. Mitochondrial function was correlated with the time course of disease-related motor behavior asymmetry and dopaminergic neuronal cell loss, respectively. Unilateral 6-OHDA injections (>2.5 μg/2 μl) into the median forebrain bundle induced an impairment of oxidative phosphorylation due to a decrease in complex I activity. This was indicated by increased flux control coefficient. During the period of days 2–21, a progressive decrease in respiratory control ratio of up to −58 % was observed in the lesioned compared to the non-lesioned substantia nigra of the same animals. This decrease was associated with a marked uncoupling of oxidative phosphorylation. Mitochondrial dysfunction, motor behavior asymmetry, and dopaminergic neuronal cell loss correlated with dosage (1.25–5 μg/2 μl). We conclude that high-resolution respirometry may allow the detection of distinct mitochondrial dysfunction as a suitable surrogate marker for the preclinical assessment of potential neuroprotective strategies in the 6-OHDA model of PD.

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Titel: 6-Hydroxydopamine impairs mitochondrial function in the rat model of Parkinson’s disease: respirometric, histological, and behavioral analyses
verfasst von: Andreas Kupsch
Werner Schmidt
Zemfira Gizatullina
Grazyna Debska-Vielhaber
Jürgen Voges
Frank Striggow
Patricia Panther
Herbert Schwegler
Hans-Jochen Heinze
Stefan Vielhaber
Frank Norbert Gellerich
Publikationsdatum: 01.10.2014
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 10/2014
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-014-1185-3

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