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Amino Acids ; 52(3): 371-385, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31902007

RESUMO

The aim of this study was to investigate the effect of the chronic administration of methionine (Met) and/or its metabolite, methionine sulfoxide (MetO), on the behavior and neurochemical parameters of young rats. Rats were treated with saline (control), Met (0.2-0.4 g/kg), MetO (0.05-0.1 g/kg), and/or a combination of Met + MetO, subcutaneously twice a day from postnatal day 6 (P6) to P28. The results showed that Met, MetO, and Met + MetO impaired short-term and spatial memories (P < 0.05), reduced rearing and grooming (P < 0.05), but did not alter locomotor activity (P > 0.05). Acetylcholinesterase activity was increased in the cerebral cortex, hippocampus, and striatum following Met and/or MetO (P < 0.05) treatment, while Na+, K+-ATPase activity was reduced in the hippocampus (P < 0.05). There was an increase in the level of thiobarbituric acid reactive substances (TBARS) in the cerebral cortex in Met-, MetO-, and Met + MetO-treated rats (P < 0.05). Met and/or MetO treatment reduced superoxide dismutase, catalase, and glutathione peroxidase activity, total thiol content, and nitrite levels, and increased reactive oxygen species and TBARS levels in the hippocampus and striatum (P < 0.05). Hippocampal brain-derived neurotrophic factor was reduced by MetO and Met + MetO compared with the control group. The number of NeuN-positive cells was decreased in the CA3 in Met + MetO group and in the dentate gyrus in the Met, MetO, and Met + MetO groups compared to control group (P < 0.05). Taken together, these findings further increase our understanding of changes in the brain in hypermethioninemia by elucidating behavioral alterations, biological mechanisms, and the vulnerability of brain function to high concentrations of Met and MetO.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Glicina N-Metiltransferase/deficiência , Hipocampo/patologia , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Metionina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Acetilcolinesterase/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/induzido quimicamente , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Animais , Catalase/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Feminino , Glutationa Peroxidase/deficiência , Glicina N-Metiltransferase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Transtornos da Memória/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Metionina/metabolismo , Metionina/toxicidade , Ratos , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Superóxido Dismutase/deficiência , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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