Atividade das oligopeptidases Ndel1 e ECA em modelo animal para a esquizofrenia frente ao tratamento com antipsicóticos

• Autor(a) principal: Nani, Joao Victor Silva [UNIFESP]
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/0013000010qdq
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6507701; https://repositorio.unifesp.br/handle/11600/52713
• topic: Oligopeptidases; Schizophrenia; Animal model; Antipsychotics; Esquizofrenia; Oligopeptidases; Sistema nervoso central; Modelo animal; Antipsicóticos

Schizophrenia (SCZ) is a mental disorder with a multifactorial origin, characterized by disturbances in cognition, regulation of the emotional state and / or behavior of the patient. Unlike most of the already known and studied diseases, the diagnosis for mental disorders is still essentially made it from clinical interviews, often leading to an erroneous diagnosis since there is a mainly symptomatic similarity of these disorders. In this context, our group has demonstrated that the neuropeptides and oligopeptidases system seems to play an important role in the pathophysiology of schizophrenia, and in the search for a better understanding of this system, the use of a good animal model is important. Spontaneously hypertensive rats (SHRs) present behavioral deficits that mimic the symptoms observed in patients, and these deficits were reversed by the use of antipsychotics employed in the clinic, making this model viable for the study of SCZrelated alterations. Ndel1 (Nuclear Distribution Element like1) and ACE (angiotensin converting enzyme I) are oligopeptidases capable of cleaving SCZrelated neuropeptides such as neurotensin (NT) that has been described as an endogenous antipsychotic. In order to validate the biochemical alterations present in this animal model and to correlate with the data obtained in the clinic, where previous studies have already demonstrated alterations in the activity of these oligopeptidases in schizophrenic patients when compared to the healthy controls, paired by sex and age, the activity of Ndel1 and ACE in serum and selected regions of the brain of SHR animals, which were compared to Wistar (NWR) control rats, against manipulations in the dopaminergic system, such as the typical (haloperidol) and atypical (clozapine) antipsychotics, as well as proschizophrenic drugs such as amphetamine and lisdexamphetamine. Significant differences in the activity of these oligopeptidases were observed, both before and after treatment with antipsychotics, which strengthen the validity of this SCZ animal model. It was also possible to observe a correlation between levels of activity in the blood (peripheral) that reflect the activity levels of most regions of the brain (central), strengthening the study using the enzymatic activity of these oligopeptidase as a tool to investigate the neurobiology of SCZ.