RESUMO
Ketogenic diets have been used to treat epilepsy in children for almost 80 years. However, there are only few studies concerning behavioral effects of these diets, besides their efficacy in treating seizure disorders induced by kainic acid or pentylenetetrazol in rats. Here, rats were fed with a ketogenic diet and locomotion, anxiety and nociception were investigated after 10 weeks. Male Wistar rats were weight matched and divided into two groups: control rats, that received regular laboratory ration, and KD rats, that received ketogenic diet (70% fat, 24% protein and no carbohydrate). Behavioral tests were applied after 10-12 weeks of treatment, and included tests to evaluate exploration (habituation to the open field), anxiety (plus-maze), and nociception (tail-flick measurement). Performance of the animals in the open field revealed a significant difference in the number of crossings, suggesting a higher locomotor activity in animals fed with a ketogenic diet. No differences in anxiety were observed, as evaluated by the plus-maze test. Nociception was measured by the latency in the tail-flick test, and ketogenic rats presented a hypernociceptive response. Yet, these animals responded to a stressor with the classic analgesia, similarly to the controls. The response of ketogenic diet fed rats to the stressor, however, was more prolonged. Exposure to a ketogenic diet may induce higher locomotor activity, together with a hypernociceptive state in the animals, possibly as a result of some alteration in the neural systems involved in the modulation of these behaviors.
Assuntos
Nível de Alerta , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Corpos Cetônicos/sangue , Aprendizagem em Labirinto , Atividade Motora , Limiar da Dor , Animais , Nível de Alerta/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Atividade Motora/fisiologia , Limiar da Dor/fisiologia , Ratos , Tempo de Reação/fisiologia , Estresse Psicológico/complicaçõesRESUMO
Ketogenic diets have been used to treat seizure disorders of children resistant to conventional anti-epileptic drug treatment. The mechanism of action of this diet, however, is unknown. Gliosis is a very common characteristic in tissues associated with epileptogenesis and glial cytokines may be involved in the pathology of seizure disorders. We investigate herein, whether ketogenic diet fed rats demonstrate changes in the immunocontent of S100B, an astrocyte-derived cytokine elevated in the temporal lobe of refractory epilepsy. Lower levels of S100B were observed in cerebrospinal fluid with no significant changes in S100B and GFAP content in brain tissue. Ketogenic fed rats presented a lower seizure severity induced by pentylenetetrazole and no change in cerebrospinal fluid S100B after pentylenetetrazole administration. These results support the concept that the ketogenic diet is neuroprotective in seizure disorders. Since S100B has an extracellular activity in neuronal excitability and synaptic plasticity, it would be reasonable to conceive that a decrease in the S100B could be involved in the mechanism of action of the ketogenic diet. However, it is not possible to establish a direct link between reduced CSF S100B and decreased severity of PTZ-induced attacks at present moment. Regardless of this, CSF S100B could be proposed as an index of efficacy of ketogenic diet for seizure disorders.
Assuntos
Epilepsia/líquido cefalorraquidiano , Epilepsia/terapia , Alimentos Formulados , Gliose/líquido cefalorraquidiano , Corpos Cetônicos/metabolismo , Proteínas S100/líquido cefalorraquidiano , Animais , Astrócitos/metabolismo , Biomarcadores , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Convulsivantes , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Epilepsia/prevenção & controle , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Fatores de Crescimento Neural , Pentilenotetrazol , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100 , Resultado do TratamentoRESUMO
The ketogenic diet (KD), characterized by high fat and low carbohydrate and protein contents, has been proposed to be beneficial in children with epilepsy disorders not helped by conventional anti-epileptic drug treatment. Weight loss and inadequate growth is an important drawback of this diet and metabolic causes are not well characterized. The aim of this study was to examine body weight variation during KD feeding for 6 wk of Wistar rats; fat mass and adipocyte cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity were also observed. PEPCK activity was determined based on the [H(14)CO(3) (-)]-oxaloacetate exchange reaction. KD-fed rats gained weight at a less rapid rate than normal-fed rats, but with a significant increment in fat mass. The fat mass/body weight ratio already differed between ketogenic and control rats after the first week of treatment, and was 2.4 x higher in ketogenic rats. The visceral lipogenesis was supported by an increment in adipocyte PEPCK, aiming to provide glycerol 3-phosphate to triacylglycerol synthesis and this fat accumulation was accompanied by glucose intolerance. These data contribute to our understanding of the metabolic effects of the KD in adipose tissue and liver and suggest some potential risks of this diet, particularly visceral fat accumulation.
Assuntos
Tecido Adiposo/anatomia & histologia , Dieta Cetogênica/estatística & dados numéricos , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Redução de Peso/fisiologia , Tecido Adiposo/efeitos dos fármacos , Animais , Criança , Colesterol/sangue , Epilepsia/prevenção & controle , Humanos , Masculino , Ratos , Ratos Wistar , Triglicerídeos/sangue , Redução de Peso/efeitos dos fármacosRESUMO
Ketogenic diets have been used to treat seizure disorders of children and recently it was shown to increase the drug-induced seizure threshold in rats. Protein phosphorylation is a major regulatory mechanism of signal transduction that has been implicated in modulating neuronal excitability. We investigated the basal protein phosphorylation in microslices from different brain regions (hippocampus, cerebral cortex and cerebellum) of young rats fed a ketogenic diet, and we evaluated the effect of this diet on weight development and health of these rats based on serum biochemistry. Thirty-day-old rats consumed ad libitum ketogenic (high fat) or control diets for 8 wk. Rats consuming the high fat diet had ketonemia without signs of undernutrition or illness. Microslices were incubated in media containing (32)P-phosphate, and (32)P-phosphoprotein content was analyzed by one- or two-dimensional electrophoresis followed by autoradiography. Basal protein phosphorylation was greater in brain slices from ketogenic rats. Different increments of synapsin I, GAP-43 and GFAP phosphorylation were observed in two-dimensional autoradiography. A ketogenic diet induced metabolic changes affecting the basal status of protein phosphorylation. This change could affect the mechanisms of signal transduction in neural cells involved in the increase in the seizure threshold.
Assuntos
Encéfalo/metabolismo , Gorduras na Dieta/administração & dosagem , Corpos Cetônicos/biossíntese , Fosfoproteínas/metabolismo , Animais , Autorradiografia , Cerebelo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Proteína GAP-43/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Glucose/farmacologia , Hipocampo/metabolismo , Corpos Cetônicos/sangue , Corpos Cetônicos/farmacologia , Masculino , Fosfatos/metabolismo , Radioisótopos de Fósforo , Fosforilação , Ratos , Ratos Wistar , Sinapsinas/metabolismoRESUMO
Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities--glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.