Expression of the immediate early genes, c-fos and egr-1, in the rat brain in the learned helplessness model

O desamparo aprendido (DA) corresponde à dificuldade de aprendizagem operante em função de exposição prévia a choques incontroláveis. Esse efeito vem sendo proposto como modelo animal de depressão e também defendido por alguns pesquisadores como modelo animal para o transtorno de estresse pós-traumático (TEPT). O objetivo do presente trabalho foi examinar a ativação dos genes c-fos e egr-1 em áreas do encéfalo de ratos submetidos ao tratamento que induz o desamparo aprendido, priorizando estruturas consideradas funcionalmente importantes para os distúrbios de aprendizagem, como a amígdala (AMI), o hipocampo (HIP) e o córtex pré-frontal medial (CPFm). Considerado importante para o desenvolvimento do desamparo aprendido por alguns autores, o núcleo septal lateral (NSL) também foi analisado. No estudo, ratos machos Wistar adultos, sujeitos do grupo Incontrolável (INC), após período de adaptação ao ambiente laboratorial, receberam 60 choques inescapáveis de 1,0 mA, 10 segundos de duração, ministrados nas patas a intervalos médios de 1 minuto. Após 24 horas, estes animais e os controles ingênuos (ING), que não receberam choques no tratamento, foram submetidos à contingência de fuga. Critérios de aprendizagem previamente estabelecidos foram aplicados para selecionar os animais do grupo ING que aprenderam, e para separar os sujeitos do grupo INC nos subgrupos dos animais que não aprenderam (DES) e dos que aprenderam normalmente (NDE). Grupos controle sem adaptação e sem choque (BIO), ou com adaptação e sem choque (ADA), também foram manipulados. Após o teste de aprendizagem, os animais foram anestesiados, perfundidos, e seus encéfalos extraídos. Os cortes dos encéfalos foram tratados para imunoperoxidase para revelar as proteínas Fos e Egr-1. Os resultados evidenciaram características distintas de expressão dos genes c-fos e egr-1 nas diferentes estruturas. Foi observado um aumento na imunorreatividade para Fos nas áreas CA1 do HIP e CPFm para o grupo ING, e uma redução do marcador Fos no CPFm do grupo DES se comparado ao grupo NDE. Um aumento na imunorreatividade para Egr-1 foi evidenciado no giro denteado (GD) do HIP do grupo DES em relação a todos os grupos, à exceção do grupo ING. Na região central da AMI o aumento para Egr- 1 ocorreu no grupo DES em relação ao grupo ING, e na região basolateral, entre o grupo DES e os grupos BIO e ING. Os coeficientes de correlação de Pearson mostraram covariação entre os dados das duas regiões da AMI e entre os dados do GD para Egr-1 e NSL para Fos e Egr-1. Também foi evidenciada uma maior correlação entre os dados dos dois marcadores no grupo DES, seguido do NDE e do ING, nesta sequência. Os dados indicam que circuitos neurais relacionados à aprendizagem e memória estão envolvidos no desenvolvimento do desamparo aprendidoThe learned helplessness (LH) phenomenon corresponds to difficulties in operant learning as a result of previous exposure to uncontrollable shocks. This effect has been suggested as an animal model of depression and posttraumatic stress disorder (PTSD). The purpose of this work was to examine the activation of c-fos and egr-1 genes in brain areas of rats exposed to treatment which induces the LH behavior, especially in some structures recognized as functionally important to learning disorders, such as the amygdala (AMI), the hippocampus (HIP), and the medial prefrontal cortex (mPFC). Cited as important to LH development the lateral septal nucleus (LSN) was also examined. In the experiment, adult male Wistar rats from the uncontrollable group (INC), after a 3-day exposure to the experimental conditions, received 60 inescapable 1.0 mA footshocks lasting 10 seconds each, applied at an average interval of 1.0 minute. After 24 hours, these animals and the naive controls (ING), which did not receive footshocks during treatment, were tested in a shuttlebox. Previously established criteria were applied to select the ING animals that learned the escape response, and also to sort the INC animals into nonlearning (DES) and learning (NDE) subgroups according to their performance during the escape test. Subjects not exposed to adaptation or footshocks (BIO), and subjects adapted but not exposed to footshocks (ADA) were also manipulated. All animals received anesthesia and after transcardiac perfusion had their brains removed, sectioned and immunohistochemically treated to reveal Fos and Egr-1 proteins. The results showed distinct attributes for c-fos and egr-1 gene expression in the brain structures examined. Data analysis revealed significantly higher Fos immunoreactivity in the HIP CA1 and mPFC in the ING group than in the other groups. A decrease was detected in Fos-positive nuclei in the DES group mPFC compared with the NDE group. An increase in the Egr-1 positive nuclei was found in the HIP dentate gyrus (DG) in the DES group compared with all the groups, except the ING group. An increment in Egr-1 imunoreactivity was also detected in the central AMI in the DES group in relation to ING group, and in the basolateral AMI in the DES group against the BIO and ING groups. Pearsons correlation test indicated covariation between data from central and basolateral AMI regions. A high correlation coefficient was found between data from DG for Egr-1 and from NSL for both Fos and Egr-1. A high correlation was observed between the two markers for the DES group, followed by the NDE and ING groups, in that sequence. The results suggest that the neural circuits underlying memory and learning are implicated in the development of the LH effec

Novelty, but Not Operant Aversive Learning, Enhances Fos and Egr-1 Expression in the Medial Prefrontal Cortex and Hippocampal Areas of Rats

Immediate early genes (IEG) are presumed to be activated in response to stress, novelty, and learning. Evidence supports the involvement of prefrontal and hippocampal areas in stress and learning, but also in the detection of novel events. This study examined whether a previous experience with shocks changes the pattern of Fos and Egr-1 expression in the medial prefrontal cortex (mPFC), the hippocampal cornus ammonis 1 (CA1), and dentate gyrus (DG) of adult male Wistar rats that learned to escape in an operant aversive test. Subjects previously exposed to inescapable footshocks that learned to escape from Shocks were assigned to the treated group (EXP). Subjects from Group Novelty (NOV) rested undisturbed during treatment and also learned to escape in the test. The nonshock group (NSH) rested undisturbed in both sessions. Standard immunohistochemistry procedures were used to detect the proteins in brain sections. The results show that a previous experience with shocks changed the pattern of IEG expression, then demonstrating c-fos and egr-1 induction as experience-dependent events. Compared with NSH and EXP an enhanced Fos expression was detected in the mPFC and CA1 subfield of Group NOV, which also exhibited increased Egr-1 expression in the mPFC and DG in comparison to NSH. No differences were found in the DG for Fos, or in the CA1 for Egr-1. Novelty, and not the operant aversive escape learning, seems to have generated IEG induction. The results suggest novel stimuli as a possible confounding factor in studies on Fos and/or Egr-1 expression in aversive conditions.CAPESCAPESFAPESPFAPESPCNPqCNP

Myoma Expulsion after Uterine Artery Embolization

Introduction. Uterine leiomyomas are the most common benign pelvic tumors in women over 35 years and can be symptomatic or asymptomatic. Among the main treatment strategies, there are hormone therapy, hysterectomy, myomectomy, and uterine artery embolization (UAE), a recent and promising treatment for patients who wish to avoid hysterectomy. Ideal candidates for UAE are women with symptomatic uterine leiomyomas that present no desire for pregnancy, premenopausal and heavy menstrual bleeding, or dysmenorrhea caused by intramural fibroids. Case Presentation. A 36-year-old female diagnosed with leiomyomas and an extensive history of failed previous treatments who, in order to preserve her uterus, underwent UAE and had tumor expulsion 15 days after the procedure. The patient remained eight months in amenorrhea and, currently, presents normal hormone levels and irregular periods. Conclusion. UAE presents itself as a minimally invasive procedure and as an efficient alternative for those patients who wish to preserve their uteri and also improve their symptoms and quality of life