Environmental Intervention As a Therapy for Adverse Programming by Ancestral Stress

Overview

Journal Sci Rep

Specialty Science

Date 2016 Nov 25

PMID 27883060

Citations 24

Authors

J Keiko McCreary

Zachary T Erickson

Yongxin Hao

Yaroslav Ilnytskyy

Igor Kovalchuk

Gerlinde A S Metz

Affiliations

Soon will be listed here.

Abstract

Ancestral stress can program stress sensitivity and health trajectories across multiple generations. While ancestral stress is uncontrollable to the filial generations, it is critical to identify therapies that overcome transgenerational programming. Here we report that prenatal stress in rats generates a transgenerationally heritable endocrine and epigenetic footprint and elevated stress sensitivity which can be alleviated by beneficial experiences in later life. Ancestral stress led to downregulated glucocorticoid receptor and prefrontal cortex neuronal densities along with precocious development of anxiety-like behaviours. Environmental enrichment (EE) during adolescence mitigated endocrine and neuronal markers of stress and improved miR-182 expression linked to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) regulation in stressed lineages. Thus, EE may serve as a powerful intervention for adverse transgenerational programming through microRNA-mediated regulation of BDNF and NT-3 pathways. The identification of microRNAs that mediate the actions of EE highlights new therapeutic strategies for mental health conditions and psychiatric disease.

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