Dados do Trabalho

Título

MATERNAL SEPARATION EFFECTS ON NEUROENDOCRINE AND ANXIETY-LIKE BEHAVIOR PARAMETERS IN ADULT BALB/C MICE

Introdução

Exposure to adverse situations in early life, such as disruption of maternal care, lead to deleterious long-term consequences. Several preclinical studies investigating early life stress effects using maternal separation (MS) models showed induced behavioral and biomolecular modifications. However, conflicting results on MS studies remain and compromise the reliability and replicability of those findings. Recent systematic reviews and meta-analytic studies addressed these issues, suggesting that the standardization of the MS protocol and outcomes based on multiple behavioral tasks can lead to much more consisting results.

Objetivo

To address that, this study aims to investigate, using a battery of classical behavioral tasks, whether MS affects anxiety-like behaviors and how MS would effect gene expression related to glucocorticoids (GR) and mineralocorticoids (MR) in the medial pre-frontal cortex (mPFC).

Método

Balb/c mice were exposed to MS from postnatal day (PND) 2 to 14 over 180-min. Two independent cohorts were ran to assess both baseline and anxiety-like behavior responses to MS at PND60. Composite scores were used to evaluate MS effects on anxiety and risk assessment phenotypes. mRNA gene expression was assessed using real-time PCR and peripheral corticosterone levels (CORT) to investigate possible neurobiological correlation to anxiety behaviors.

Resultados

MS differently affect anxiety-like phenotype and risk assessment behaviors. MS mice showed increased anxiety-like response and decreased risk assessment and exploration behaviors. These results were followed by a decrease on MR mRNA expression and higher levels of CORT induced by MS protocol.

Conclusão

Our findings strengthen the body of evidence suggesting long-term MS consequences on anxiety and risk assessment phenotypes following the exposure to a standardized MS protocol. MS exposure affected the expression of MR mRNA and induced significant changes on CORT response. These results highlight that the reprograming MS effects on the HPA axis could be mediated through MR gene expression in the mPFC and through the overactivity of peripheral CORT levels.

Palavras-chave

early life stress; anxiety-like behavior; maternal separation