Papel dos hormônios estrogênio e progesterona durante o status epilepticus no modelo de lítio-pilocarpina em Proechimys

• Ano de defesa: 2019
• Autor(a) principal: Calvo, Viviam Sofia Sanabria [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Estrous Cycle; Hormones; Epilepsy; Pilocarpine; Proechimys; Ciclo Estral; Hormônios; Epilepsia; Pilocarpina
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=8001257; https://repositorio.unifesp.br/handle/11600/59905

The neotropical rodent Proechimys guyannensis (P. guyannensis) has aroused interest in neuroscience due to scientific studies suggesting resistance of these animals to the development of epilepsy in experimental models of temporal lobe epilepsy. However, their physiology is still unknown and studies are mostly done on males. Including female animals in basic studies is relevant to make a study translational. Aims: In the first part of the study, our objective was to characterize the estrous cycle of P. guyannensis rodents. In a second part, our objective was to verify at biochemical, hormonal and cytochemical levels, the effect of pilocarpine on the induction of status epilepticus (SE) in female P. guyannensis. Methodology: In the first part, vaginal smears and characterization of vaginal membrane states were used to determine the estrous cycle. Hormonal analysis and isolation of females were performed to verify the relationship with the estrous cycle. In a second stage of the study, we performed lithium-pilocarpine ramp-up SE induction and collected blood serum at 30 and 90 minutes in SE. In parallel, we analyzed oophorectomized (OVX) P.guyannensis to perform comparative analyzes with non- oophorectomized sham females (NOVX). Additionally, we evaluated the expression and colocalization of estrogen receptors (alpha and beta), progesterone, GABAB and mGluR2 / 3. Results: P.guyannensis have estrous cycles lasting 9 to 10 days, with the shortest estrous phase (1 day) and the longest metestrus (3-4 days). These females are able to cycle even in the absence of males, and their vaginal membranes do not follow the cycles and may be closed during fertile periods (estrus phase). Progesterone and estrogen levels are higher in the proestrus phase. In the second part of the study, our data show that SE latency was similar to that observed in other rodents, but the amount of pilocarpine required to induce SE in female Proechimys was higher (100 times or more). During SE, Proechimys evolved only to stage 2 on the Racine scale. These data may suggest some resistance of female Proechimys to SE induction. Regarding biochemical and hormonal analyzes, glucose and progesterone increased at 30 min in SE and returned to normal levels xix at 90 min in SE. The estrogen receptor alpha expression in the Proechimys hippocampus was higher than the beta receptor expression in control animals, but at 90 min in SE, a higher beta expression was observed. Conclusion: Our study is the first to induce SE in female P. guyannensis. and in analyze hormonal and biochemical parameters in these rodents at 30 and 90 min after SE. Females are more resistant to SE than males. We can speculate if the increases in progesterone and/or glucose during SE are part of compensatory mechanism of the organism of these animals.