Cystamine and ethyl-eicosapentaenoic acid treatment fail to prevent malonate-induced striatal toxicity in mice.
Neurobiol Aging
; 32(12): 2326.e1-4, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21741126
ABSTRACT
Cystamine has demonstrated neuroprotective activity in a variety of studies, and is currently being evaluated in a human clinical trial in Huntington's disease (HD). Cystamine treatment of various genetic models of HD demonstrated protection against neurodegeneration and/or improvement in behavior. Given the need for a rapid screening tool for HD therapeutics, we assessed the potential therapeutic benefits of cystamine in a short-term acute toxicity murine model of striatal cell death. Cystamine did not provide neuroprotection against bilateral intrastriatal malonate injections in mice as measured by lesion size, loss of striatal volume, or decreased striatal neuronal counts. Similar results were obtained for treatment with another potential therapeutic agent that was protective in genetic mouse models of HD, the essential fatty acid ethyl-eicosapentaenoic acid. Our findings suggest that this toxic model is not reflective or predictive of findings in genetic mouse models, and may not be useful as a preclinical screen for HD therapeutics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Eicosapentaenoico
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Fármacos Neuroprotetores
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Corpo Estriado
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Cistamina
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Modelos Animais de Doenças
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Malonatos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA