Efeito do fotoperíodo no status epilepticus e epileptogenese

• Ano de defesa: 2018
• Autor(a) principal: Marques, Thalita Ewellyn Batista Sales
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Alagoas; Brasil; Programa de Pós-Graduação em Ciências da Saúde; UFAL
• Palavras-chave em Português: Epilepsia do lobo temporal; Epilepsia reflexa fotossensível; Claro constante; Escuro constante; Status epilepticus; Temporal lobe epilepsy; Epilepsy, Reflex; Constant light; Constant dark; CNPQ::CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://www.repositorio.ufal.br/handle/riufal/6040

There is strong evidence that epileptic seizures occur in diurnal patterns of 24 hours. Changes in exposure time to light/dark cycles are likely to interfere with the susceptibility of epileptic seizures in animal models of experimental epilepsy. The interaction between mesial Temporal Lobe Epilepsy (mTLE) and the circadian rhythm is shown through the rhythmicity of the seizures, daytime’s effect on seizure onset and the efficacy of antiepileptic drugs. However, knowledge about the relationship between circadian rhythm and epilepsy or epileptic seizures still limited. In this study, we investigated the effect of constant light and constant dark on status epilepticus (SE) and epileptogenesis. For this, we alter the circadian rhythm of the animals through the constant light and constant dark and use the experimental model of TLE induced by pilocarpine. Male Wistar rats were assigned to the following experimental groups: i) Animals conditioned at 24 hours of constant light for two weeks; ii) Animals conditioned at 24 hours of constant dark for two weeks; iii) Animals conditioned at 12 hours of light and 12 hours of darkness for two weeks. For each group, we evaluated a) latency for SE and severity of epileptic seizures during SE; and b) gene expression of circadian molecular clock genes and genes that participate in the epileptogenic process by RT-qPCR; c) neurodegeneration of SE in the animals' hippocampus by immunohistochemistry and stereology; d) activity of antioxidant enzymes (SOD, Catalase and GPx); e) the total thiol content (SH); f) mitochondrial respiration; and g) Mitochondrial Membrane Potential. The results showed that animals conditioned to the constant light presented an increase in the latency time for the SE and the animals of the constant light or dark group presented decrease in seizure severity during SE. We observed changes in the levels of gene expression of both circadian rhythm regulating genes (Clock, Bmal, Cry1, Cry2, Per1, and Per3) and genes which are known to be part of the epileptogenic process (Npy, Gad65, Gad67, TNFα, and Gfap). The typical neurodegeneration resulting from SE was reduced in animals kept under constant light. By analyzing the activity of antioxidant enzymes, we found that SOD activity increases in the constant light or dark 24h post-SE goups. However, there is a decrease in the levels of thiols (SH), which means an increase of oxidized thiols and ROS production in the light/light and dark/dark groups in comparison to the naïve light/dark group. Conversely, bioenergetic data show that there is no dysfunction in mitochondrial respiration. However, in the animals of the LL-24h group, there is a loss of mitochondrial membrane potential faster than in the animals of the LD-24h group. These results show that the exposure of animals to constant light or dark decreases the severity of seizures during SE and changes the expression pattern of genes regulating the endogenous molecular clock, and genes that participate in the epileptogenic process and the constant light or dark active part of the antioxidant system and does not affect the respiratory control of mitochondria.