Estudo dos efeitos neuroprotetores do ômega-3, liraglutide, risperidona e clozapina em um modelo neuroinflamatório induzido por Poly I:C em cultura primária de células hipocampais

Abstract

Exposing the brain to immune challenges during critical periods of development leads to lasting changes. It is known that exposure to pathogens during perinatal period is related to the development of inflammatory processes which lead to the development of neurodevelopmental disorders such as autism and schizophrenia. Currently, animal models of schizophrenia immune challenge, pre- or neonatal, have gained much evidence. One of these models involves perinatal administration of virus mimetic poly I: C. The mechanisms underlying the immune challenge by poly I: C in newborn animals are not fully understood, which are of great importance to the development of strategies for preventing neurodevelopmental disorders at early ages. In this context, the aim of this study was to evaluate the neuroprotective effects of omega-3, liraglutide, risperidone or clozapine in preventing neuroinflammatory changes in cultured hippocampal neural cells exposed to poly I: C. The hippocampal cells of Swiss mice were obtained from animals on the first day of birth (P0) and subjected to poly I: C alone and simultaneously treated with omega-3, liraglutide, risperidone or clozapine and incubated for 72 hours. Immersed cells only through neurobasal culture enriched with B27 supplement were used as control. Cell viability was determined by MTT test. The following parameters were evaluated according to the techniques in parentheses: NFkBp50 and inducible nitric oxide synthase -iNOS (immunofluorescence), NFkBp65 (immunoblot), nitrite (Griess method), interleukin 6 - IL-6 and brain-derived neurotrophic factor - BDNF (ELISA). The results showed that neural cells treated with Poly I: C had a significant increase NFKBp65, NFKBp50, iNOS, nitrite and IL-6 significantly decreased these parameters in the animals treated concomitantly with poly I: C + omega - 3 or poly I: C + Liraglutide also been observed that the supernatant of cultures of hippocampal neurons exposed to the omega-3 showed an high amount of expression of brain-derived neurotrophic factor - BDNF. Atypical antipsychotics clozapine and risperidone also demonstrated decreased a reduction of these parameters. The results of this study indicate that exposure of hippocampal cells to the virus mimetic poly I: C leads to possible development of cell death either by necrosis and by apoptosis and concomitant adiminstração omega -3 or liraglutide following the protocol prevention revealed an effect neuroprotective effect that this involves the reduction in iNOS expression, decreasing production of nitric oxide by inhibiting the activation of p50 and p65 subunits of NFkB transcription factor. In addition there was a decrease in IL-6 production in addition to omega-3 appears to have its dependent effect of BDNF production.