Overhauser-enhanced magnetic resonance imaging characterization of mitochondria functional changes in the 6-hydroxydopamine rat model.
Neurochem Int
; 59(6): 804-11, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21871513
Oxidative stress may be involved in the dopaminergic neurodegenerations seen in 6-OHDA-lesioned rats through its production of free radicals and through mitochondrial dysfunction. In this study, we noninvasively demonstrate brain redox alterations in 6-OHDA-lesioned rats using Overhauser-enhanced magnetic resonance imaging (OMRI). The reduction rate of 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-l-oxyl (methoxycarbonyl-PROXYL), a redox-sensitive contrast agent, was used as an index of the redox status in vivo. The methoxycarbonyl-PROXYL reduction rate, calculated from continuous images, decreased significantly in lesioned hemispheres compared to their corresponding contralateral hemispheres. The reduction rates in cellular fractions obtained from the striatum were estimated by X-band electron spin resonance (ESR) and calculated by assuming first-order kinetics for their time-dependent decreases. When methoxycarbonyl-PROXYL was mixed with cytoplasm fractions, the reduction rates were the same in both hemispheres. However, the ESR signal of methoxycarbonyl-PROXYL in the mitochondrial fraction of the lesioned hemispheres decayed more slowly than that of the corresponding contralateral hemispheres. Concordantly, biochemical assays showed that the activity of mitochondrial complex I also decreased more slowly in lesioned hemispheres. Thus, this method of noninvasively imaging brain redox alterations faithfully reflects changes in mitochondrial complex I activity in 6-OHDA-lesioned rats.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
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Oxidopamina
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Estresse Oxidativo
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Corpo Estriado
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Transtornos Parkinsonianos
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Modelos Animais de Doenças
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Metabolismo Energético
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Mitocôndrias
Limite:
Animals
Idioma:
En
Revista:
Neurochem Int
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão
País de publicação:
Reino Unido