Avaliação da expressão de c-Fos em diferentes modelos de indução de crise

Abstract

The central occurrence in the lives of people with epilepsy is the recurrence of epileptic seizures. Seizures are transient episodes characterized by signs and symptoms caused by abnormal and excessive neuronal activity. This study aimed to understand which neural structures participate in different types of seizures. For this, we used three animal models of seizures: pentylenetetrazole (PTZ, which blocks GABAergic neurotransmission), pilocarpine (PIL, muscarinic agonist), and kainic acid (KAI, glutamatergic receptor agonist). Our interest was to evaluate the pattern of neuronal activation through the presence of an immediate expression gene - c-fos, in seizures induced by different neurotransmission systems. The c-Fos protein is rapidly produced in response to neuronal activity, and its expression is localized and transient. Thus, we evaluated the amount of c-Fos+ cells in the hippocampus, cortex, thalamus, hypothalamus, and amygdala. The results showed significant differences between the models of induced seizures, with a considerable increase in c-Fos+ cells in the subregions of the hippocampus (especially the dentate gyrus), amygdala, piriform cortex, and hypothalamic nuclei. The PIL and KAI groups had more c-Fos+ cells in both hemispheres than the PTZ group in these areas. The animals in the PTZ group had shorter and less severe seizures than the PIL and KAI animals. Pre-treatment with diazepam abolished the occurrence of seizures and the presence of c-Fos+ cells after PTZ. Animals in the control group (treated with saline) did not show significant c-Fos expression. Our results suggest a strong association between seizure intensity/severity and c-Fos expression in cortical and subcortical regions. Future studies with more animals combined with immunohistochemistry for other neuronal proteins will be necessary to understand better the neural networks associated with the genesis, propagation, maintenance, and termination of seizures.