Postnatal impoverished housing impairs adolescent risk-assessment and increases risk-taking: A sex-specific effect associated with histone epigenetic regulation of Crfr1 in the medial prefrontal cortex

PSYCHONEUROENDOCRINOLOGY

卷:99

Article

Viola, Thiago Wendt¹  Wearick-Silva, Luis Eduardo¹  Creutzberg, Kerstin C.¹  Kestering-Ferreira, Erika¹  Orso, Rodrigo¹  Centeno-Silva, Anderson¹  Albrechet-Souza, Lucas²  Marshall, Paul R.³  Li, Xiang³  Bredy, Timothy W.³  Riva, Marco A.⁴  Grassi-Oliveira, Rodrigo¹ 

[1] Pontifical Catholic Univ Rio Grande do Sul PUCRS, Brain Inst InsCer, Dev Cognit Neurosci Lab, Porto Alegre, RS, Brazil

[2] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA USA

[3] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[4] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy

关键词: Stress;    Psychological;    Prefrontal cortex;    Decision making;    Risk assessment;    Epigenetics;    Histories;   

DOI  :  10.1016/j.psyneuen.2018.08.032

来源: Elsevier

【 摘 要 】

While increasing evidence posits poor decision-making as a central feature of mental disorders, very few studies investigated the effects of ear1y-life stress (EIS) on specific components of reward-related choice behaviors. Risk taking (RT) involves the exposure to some danger, or negative consequences, in order to achieve a goal-directed behavior. Such behaviors are likely to be preceded by risk-assessment (RA), which is a dynamic cognitive process involving the acquisition of information in potentially dangerous situations. Here, we investigated the effects of being raised in impoverished housing conditions during ear1y life (P2-P9) on RT, RA and dopaminergic and corticotrophinergic gene expression of adolescent male and female mice. Phenotypes were assessed by two protocols: the elevated plus-maze (EPM) and the predator-odor risk-taking (PORT). We found decreased RA in mice exposed to impoverished housing in the absence of a reward (EPM), with a more pronounced effect among females. Moreover, when exposed to a predatory olfactory cue, increased RT was observed in these females in a reward-related task (PORT), as well as decreased HPA axis responsivity. This sex-specific behavioral effect was associated with increased Crfr1 mRNA expression in the medial prefrontal cortex (mPFC) and higher levels of the histone mark H3Ft2(me2s), a histone modification known to be involved in transcriptional activation, within the promoter of the Crfr1 gene. These findings revealed that ELS exposure can impair the acquisition of environmental information in dangerous situations and increase RT in reward-related scenarios among females, with an important role regarding epigenetic regulation of the Crfr1 gene.

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