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

Autor: Frank Striggow, Grazyna Debska-Vielhaber, Jürgen Voges, Frank N. Gellerich, Patricia Panther, Andreas Kupsch, Stefan Vielhaber, Hans-Jochen Heinze, Herbert Schwegler, Werner Schmidt, Zemfira Gizatullina
Rok vydání: 2014
Předmět:
Male
Parkinson's disease
pathology [Dopaminergic Neurons]
drug effects [Dopaminergic Neurons]
Mitochondrion
physiology [Cell Death]
Oxidative Phosphorylation
Functional Laterality
Rats
Sprague-Dawley
drug effects [Medial Forebrain Bundle]
drug effects [Oxidative Phosphorylation]
Cell Death
Dopaminergic
drug effects [Mitochondria]
Immunohistochemistry
Mitochondria
Psychiatry and Mental health
physiology [Motor Activity]
Neurology
physiopathology [Parkinsonian Disorders]
medicine.drug
medicine.medical_specialty
Tyrosine 3-Monooxygenase
Substantia nigra
Motor Activity
Biology
Neuroprotection
Parkinsonian Disorders
Dopamine
Internal medicine
medicine
Animals
physiology [Mitochondria]
ddc:610
physiology [Dopaminergic Neurons]
Oxidopamine
Biological Psychiatry
pathology [Medial Forebrain Bundle]
Hydroxydopamine
Dose-Response Relationship
Drug
Pars compacta
Dopaminergic Neurons
drug effects [Motor Activity]
physiopathology [Medial Forebrain Bundle]
Medial Forebrain Bundle
drug effects [Cell Death]
medicine.disease
toxicity [Oxidopamine]
metabolism [Tyrosine 3-Monooxygenase]
Endocrinology
nervous system
Neurology (clinical)
Neuroscience
Zdroj: Journal of neural transmission 121(10), 1245-1257 (2014). doi:10.1007/s00702-014-1185-3
ISSN: 1435-1463
0300-9564
DOI: 10.1007/s00702-014-1185-3
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: