Limits...
Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Ancestral stress reduced prefrontal cortex thickness.(A) Image of a representative cresyl violet-stained coronal brain section corresponding to 3.70 mm relative to bregma illustrating the measurements of cortical thickness (DV: Dorsoventral, ML: Mediolateral, RF: Rhinal fissure, scale bar represents 2 mm). The right portion shows the gray scale 8-bit image used for mean gray value analysis. (B) DV thickness and (C) mean gray value were significantly decreased due to transgenerational and multigenerational stress, with no significant effect of enrichment therapy. PFC, prefrontal cortex. Asterisks denote significances (*p < 0.05, ***p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5121646&req=5

f3: Ancestral stress reduced prefrontal cortex thickness.(A) Image of a representative cresyl violet-stained coronal brain section corresponding to 3.70 mm relative to bregma illustrating the measurements of cortical thickness (DV: Dorsoventral, ML: Mediolateral, RF: Rhinal fissure, scale bar represents 2 mm). The right portion shows the gray scale 8-bit image used for mean gray value analysis. (B) DV thickness and (C) mean gray value were significantly decreased due to transgenerational and multigenerational stress, with no significant effect of enrichment therapy. PFC, prefrontal cortex. Asterisks denote significances (*p < 0.05, ***p < 0.001).

Mentions: Figure 3B summarizes the stress- and enrichment-associated changes in medial-lateral cortical thickness in the PFC. There was a significant effect of stress on dorsoventral thickness (F(2,103) = 8.701, p < 0.001), indicating that stressed animals had diminished cortical thickness (Fig. 3A, Left, DV). There was no significant effect of enrichment on dorsoventral cortical thickness as well as no significant effect of stress or enrichment on mediolateral thickness.


Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress
Ancestral stress reduced prefrontal cortex thickness.(A) Image of a representative cresyl violet-stained coronal brain section corresponding to 3.70 mm relative to bregma illustrating the measurements of cortical thickness (DV: Dorsoventral, ML: Mediolateral, RF: Rhinal fissure, scale bar represents 2 mm). The right portion shows the gray scale 8-bit image used for mean gray value analysis. (B) DV thickness and (C) mean gray value were significantly decreased due to transgenerational and multigenerational stress, with no significant effect of enrichment therapy. PFC, prefrontal cortex. Asterisks denote significances (*p < 0.05, ***p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121646&req=5

f3: Ancestral stress reduced prefrontal cortex thickness.(A) Image of a representative cresyl violet-stained coronal brain section corresponding to 3.70 mm relative to bregma illustrating the measurements of cortical thickness (DV: Dorsoventral, ML: Mediolateral, RF: Rhinal fissure, scale bar represents 2 mm). The right portion shows the gray scale 8-bit image used for mean gray value analysis. (B) DV thickness and (C) mean gray value were significantly decreased due to transgenerational and multigenerational stress, with no significant effect of enrichment therapy. PFC, prefrontal cortex. Asterisks denote significances (*p < 0.05, ***p < 0.001).
Mentions: Figure 3B summarizes the stress- and enrichment-associated changes in medial-lateral cortical thickness in the PFC. There was a significant effect of stress on dorsoventral thickness (F(2,103) = 8.701, p < 0.001), indicating that stressed animals had diminished cortical thickness (Fig. 3A, Left, DV). There was no significant effect of enrichment on dorsoventral cortical thickness as well as no significant effect of stress or enrichment on mediolateral thickness.

View Article: PubMed Central - PubMed

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.

No MeSH data available.