RESUMO
The Repressor Element-1 Silencing Transcription factor or Neuron-Restrictive Silencer Factor (REST/NRSF) is a zinc finger repressor transcription factor of the Kruppel family. Several studies in experimental models have shown that overexpression of REST/NRSF occurs after the induction of seizures. In the present study, the expression of REST/NRSF (messenger ribonucleic acid (mRNA) and protein) was evaluated in the hippocampus of 28 patients with drug-resistant mesial temporal lobe epilepsy (MTLE) and their correlation with clinical variables and comorbid anxiety and depression. The REST/NRSF protein expression was augmented in an age-dependent manner in the hippocampus of autopsied subjects. However, this condition was not observed in patients with MTLE, in whom overexpression of this transcription factor occurred at both the mRNA and protein levels. The correlations with clinical variables showed that the frequency of epileptic seizures was proportional to the protein expression of REST/NRSF. The results revealed that the overexpression of REST/NRSF was more evident in patients with MTLE without anxiety and depression. Our data indicate that the expression of REST/NRSF is modified in patients with MTLE. This condition has implications in the pathophysiology of this disorder, making it a potential candidate for the optimization of clinical treatments.
Assuntos
Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Proteínas Repressoras/metabolismo , Adolescente , Adulto , Ansiedade/complicações , Ansiedade/genética , Ansiedade/metabolismo , Depressão/complicações , Depressão/genética , Depressão/metabolismo , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/genética , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/genética , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Repressoras/genética , Adulto JovemRESUMO
Epilepsy is associated with several epigenetic changes, such as DNA methylation, histone modification, and alterations in the synthesis and functioning of non-coding RNAs (ncRNAs). Paradoxically, antiepileptic drugs (AEDs) that are widely used to control epilepsy may also induce epigenetic modifications and alter the structure of chromatin. As a consequence, changes in the expression of various factors involved in the pathology of epilepsy may positively or negatively affect the course of the disease. It should be noted that while AEDs are widely used in the treatment of epilepsy and other neurological disorders, many of their epigenetic consequences are still unknown. Moreover, an improved understanding of AED-induced epigenetic alterations could provide new targets for future therapeutic interventions. In this review, we give a general overview of the current scientific evidence concerning the epigenetic effects of AEDs that are currently in clinic use and have been evaluated to date.