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2.
PLoS One ; 8(4): e61626, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23620776

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease characterised by loss of motor neurons that currently has no cure. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have many health benefits including neuroprotective and myoprotective potential. We tested the hypothesis that a high level of dietary EPA could exert beneficial effects in ALS. The dietary exposure to EPA (300 mg/kg/day) in a well-established mouse model of ALS expressing the G93A superoxide dismutase 1 (SOD1) mutation was initiated at a pre-symptomatic or symptomatic stage, and the disease progression was monitored until the end stage. Daily dietary EPA exposure initiated at the disease onset did not significantly alter disease presentation and progression. In contrast, EPA treatment initiated at the pre-symptomatic stage induced a significantly shorter lifespan. In a separate group of animals sacrificed before the end stage, the tissue analysis showed that the vacuolisation detected in G93A-SOD1 mice was significantly increased by exposure to EPA. Although EPA did not alter motor neurone loss, EPA reversed the significant increase in activated microglia and the astrocytic activation seen in G93A-SOD1 mice. The microglia in the spinal cord of G93A-SOD1 mice treated with EPA showed a significant increase in 4-hydroxy-2-hexenal, a highly toxic aldehydic oxidation product of omega-3 fatty acids. These data show that dietary EPA supplementation in ALS has the potential to worsen the condition and accelerate the disease progression. This suggests that great caution should be exerted when considering dietary omega-3 fatty acid supplements in ALS patients.


Assuntos
Esclerose Lateral Amiotrófica/patologia , Progressão da Doença , Ácido Eicosapentaenoico/efeitos adversos , Administração Oral , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/fisiopatologia , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Axônios/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Proteínas Mutantes/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/patologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Análise de Sobrevida , Tirosina/análogos & derivados , Tirosina/metabolismo , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo
3.
Amyotroph Lateral Scler ; 10(4): 221-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19308767

RESUMO

It has been shown that chronic treatment with lithium carbonate (Li(2)CO(3)) in presymptomatic SOD1G93A transgenic male mice, a model of ALS, was able to remarkably increase their lifespan through the activation of autophagy and the promotion of mitochondriogenesis and neurogenesis. This prompted us to test the lithium effect also in female SOD1G93A mice with two phenotypes of different disease severity. Female SOD1G93A mice of C57BL/6J or 129S2/Sv genetic background were treated daily with Li(2)CO(3) 37 mg/kg (1 mEq/kg) i.p. starting from age 75 days until death. Grip strength, latency to fall on rotarod and body weight were monitored twice weekly. At the time of death the spinal cord was removed to assess the number of motor neurons and to measure the expression of a marker of autophagy (LCII) and the activity of mitochondrial complex IV. We observed a significant anticipation of the onset and reduced survival in 129Sv/G93A and no effect in C57/G93A mice treated with lithium compared to vehicle treated mice. Moreover, lithium neither exerted neuroprotective effects nor increased the expression of LCII and the activity of mitochondrial complex IV in the spinal cord. The present study does not identify any therapeutic or neuroprotective effect of lithium in SOD1G93A female mice.


Assuntos
Esclerose Lateral Amiotrófica , Antimaníacos/uso terapêutico , Carbonato de Lítio/uso terapêutico , Superóxido Dismutase , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/veterinária , Animais , Antimaníacos/farmacologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Biomarcadores/metabolismo , Peso Corporal , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Carbonato de Lítio/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Medula Espinal/metabolismo , Medula Espinal/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Taxa de Sobrevida
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