RESUMO
The ketogenic diet (KD) is a high-fat, low-protein and low-carbohydrate diet included as medical practice against seizure disorders, particularly in children refractory to conventional anti-epileptic drug treatment. However, the molecular basis of its therapeutic effect remains unclear. Considering the growing evidence for the importance of glial cells for neuronal development, survival and plasticity, we investigated astrocyte protein markers from KD fed rats, in different regions of hippocampus, a brain structure commonly involved in seizure disorders. We found a transitory increment in GFAP in the CA3 hippocampal region, but not in the CA1 or dentate gyrus (DG). This change was not accompanied by changes in S100B content or glutamine synthetase activity. In order to evaluate possible hippocampal involvement we investigated spatial-cognitive behavior using the water-maze task. No changes were observed. This transitory gliosis in CA3 could be related to, or precede, other associated changes proposed to be involved in the attenuation of seizure disorders. These data reinforce the importance of hippocampal astrocytes as cell targets during KD feeding.
Assuntos
Dieta com Restrição de Carboidratos , Dieta com Restrição de Proteínas , Gorduras na Dieta/administração & dosagem , Gliose/etiologia , Hipocampo/patologia , Animais , Astrócitos/patologia , Astrócitos/fisiologia , Epilepsia/dietoterapia , Proteína Glial Fibrilar Ácida/análise , Gliose/patologia , Glutamato-Amônia Ligase/metabolismo , Hipocampo/química , Corpos Cetônicos/sangue , Masculino , Fatores de Crescimento Neural/análise , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/análiseRESUMO
The S100B protein belongs to a family of small Ca2+-binding proteins involved in several functions including cytoskeletal reorganization. The effect of S 100B on protein phosphorylation was investigated in a cytoskeletal fraction prepared from immature rat hippocampus. An inhibitory effect of 5 microM S100B on total protein phosphorylation, ranging from 25% to 40%, was observed in the presence of Ca2+ alone, Ca2+ plus calmodulin or Ca2+ plus cAMP. Analysis by two dimensional electrophoresis revealed a Ca2+/calmodulin-dependent and a Ca2+/cAMP-dependent inhibitory effect of S100B, ranging from 62% to 67% of control, on the phosphorylation of the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. The fact that S100B binds to the N-terminal domain of GFAP and that the two proteins are co-localized in astrocytes suggests a potential in vivo role for S100B in modulating the phosphorylation of intermediate filament proteins in glia.