RESUMO
BACKGROUND: Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. PURPOSE: We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. METHOD: Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. RESULTS: Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. CONCLUSIONS: Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.
Assuntos
Senilidade Prematura/dietoterapia , Senilidade Prematura/patologia , Encéfalo/patologia , Morte Celular , Suplementos Nutricionais , Vitamina E/administração & dosagem , Senilidade Prematura/metabolismo , Animais , Peso Corporal , Encéfalo/metabolismo , Morte Celular/fisiologia , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Ingestão de Alimentos , Endonucleases/deficiência , Endonucleases/genética , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Fatores de Tempo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Tremor/dietoterapia , Tremor/metabolismo , Tremor/patologia , Vitamina E/metabolismoRESUMO
OBJECTIVE: This study investigated the relationship between outcome and structural brain abnormalities in schizophrenia. METHOD: Intracranial volume and volumes of the cerebrum, gray and white matter, lateral and third ventricles, frontal lobes, thalamus, and cerebellum were measured in 20 patients with a poor outcome, 25 with a favorable outcome, and 23 healthy comparison subjects with magnetic resonance imaging. RESULTS: Thalamic volume was significantly smaller both in poor-outcome patients and good-outcome patients. In contrast, only poor-outcome patients displayed significantly smaller cerebral gray matter, particularly prefrontal, and enlargement of the lateral and third ventricles. No significant differences were found for intracranial, cerebellar, or cortical CSF volumes. CONCLUSIONS: Smaller thalamic volumes in schizophrenia may reflect a greater susceptibility for the disorder and seem unrelated to outcome. In contrast, gray matter volume loss of the cerebrum, particularly in the frontal lobes, and lateral and third ventricular enlargement appear related to outcome in schizophrenia.