Exposição a enriquecimento ambiental durante a periadolescência previne alterações comportamentais em um modelo animal de esquizofrenia: possível participação do BDNF

• Ano de defesa: 2016
• Autor(a) principal: Santos, Camila Mauricio [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: SHR; Esquizofrenia; Modelo animal; Enriquecimento ambiental; BDNF
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3532216; http://repositorio.unifesp.br/handle/11600/47786

Schizophrenia is a highly disabling mental disorder with complex and multifactorial etiology. Its pathophysiology is not completely elucidated, but changes in brain-derived neurotrophic factor (BDNF) appear to be associated. Treatments are symptomatic and limited, having serious side effects. Much has been thought about preventive strategies, but that doesn?t endanger individuals that will not develop the disease. In this study, we used the SHR (Spontaneously Hypertensive Rats) strain as schizophrenia model, and environmental enrichment (EE) as a possible neuroprotective and preventive environmental intervention. Aim: To evaluate the effect of early exposure to EE in behaviors related to schizophrenia, in parameters related to BDNF and in number of neurons and synapsis in SHR strain. Methods: Wistar (control) and SHR rats were exposed to an EE protocol since weaning (21 postnatal days) for 6 weeks. We performed the following behavioral tests in animals when they reached adulthood: spontaneous alternation (evaluates working memory), locomotion in open field (positive symptoms), social interaction (negative symptoms), prepulse inhibition of startle - PPI (sensory-motor processing) and contextual fear conditioning (emotional processing). In parallel, we evaluated the profile of factors related to BDNF in adult animals not exposed to EE (amount of different isoforms and receptors). Also, we investigated the number of neurons and synapses in prefrontal-cortex, striatum and hippocampus and BDNF levels in prefrontal cortex and hippocampus in order to verify possible changes in these parameters due to exposure to EE. Results: We observed in SHR animals not exposed to EE behavioral changes expected for the schizophrenia model. SHRs that were exposed to the enrichment showed behavior similar as Wistar in spontaneous alternation test, locomotion, PPI and contextual fear conditioning, but not in the social interaction test. We also observed an increase in the amount of BDNF in the hippocampus of SHR animals that was prevented by EE exposition and an increase in the number of neurons in the hippocampus of all animals exposed to EE. Conclusions: early exposure to EE was able to prevent cognitive deficits, but not negative symptoms, causing no impairment in Wistar. Moreover, this protocol increased number of neurons in hippocampus of both strains and prevented increase in BDNF that seem to be deleterious for SHR animals. Thus, EE can be a safe and effective strategy in preventing some symptoms of schizophrenia and the comprehension of its molecular mechanisms of action can be useful for the development of new strategies in treating the disease.