Desafio imune neonatal em camundongos Balb/c: influência do sexo em alterações comportamentais e expressão hipocampal de genes associados ao neurodesenvolvimento e esquizofrenia

Abstract

Schizophrenia, one of the most serious mental health conditions, has a diverse and complex symptomatology and varies greatly between the sexes. Positive symptoms include delusions and hallucinations, while negative symptoms include anhedonia, depression and social isolation. Cognitive symptoms, such as memory and concentration deficits, further complicate the clinical picture. In addition, patients may present additional physiological and behavioral disorders. The aims of this study include determining the behavioral and developmental changes in male and female mice submitted to the postnatal immune challenge-induced schizophrenia model, evaluating the expression of non-genomic estrogen receptors (GPER1) and intracellular signaling proteins related to the activation of these receptors in the hippocampus of adult mice. The study was conducted with albino mice (Mus musculus, Balb/C strain), subjected to neonatal immune challenge with Poly I:C in the PN5-PN7 period. Weight, physical developmental milestones, auscultation reflex and straightening reflex were assessed, as well as behavioral assessments using the open field, social interaction, elevated cross maze and prepulse inhibition (PPI) tests. The expression of mRNA was determined using the qPCR technique to analyze inflammatory markers and signaling pathways. Preliminary results indicate that neonatal immune challenge with Poly I:C induces behavioral changes that mimic the symptoms of schizophrenia, especially in female mice. Female-Poly I:C mice showed reduced social and exploratory behavior, reduced pre-pulse inhibition and impairment in the straightening and auscultation reflexes, while male-Poly I:C mice showed impairment only in the straightening reflex. IGF1 gene expression was increased in Poly I:C females, while RELA gene expression was increased in both males and females exposed to neonatal immune challenge. The modulation of these receptors may represent an innovative approach to the treatment of schizophrenia, not only with regard to behavioral symptoms, but also to the underlying neuroinflammatory processes. These findings may contribute to the development of new molecules and to a therapeutic approach that differs between men and women, offering an innovative strategy for the treatment of schizophrenia.