Dataset Information

Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.

ABSTRACT:

Background

Pathological anxiety originates from a complex interplay of genetic predisposition and environmental factors, acting via epigenetic mechanisms. Epigenetic processes that can counteract detrimental genetic risk towards innate high anxiety are not well characterized.

Methods

We used female mouse lines of selectively bred high (HAB)- vs low (LAB)-innate anxiety-related behavior and performed select environmental and pharmacological manipulations to alter anxiety levels as well as brain-specific manipulations and immunohistochemistry to investigate neuronal mechanisms associated with alterations in anxiety-related behavior.

Results

Inborn hyperanxiety of high anxiety-like phenotypes was effectively reduced by environmental enrichment exposure. c-Fos mapping revealed that hyperanxiety in high anxiety-like phenotypes was associated with blunted challenge-induced neuronal activation in the cingulate-cortex, which was normalized by environmental enrichment. Relating this finding with epigenetic modifications, we found that high anxiety-like phenotypes (compared with low-innate anxiety phenotypes) showed reduced acetylation in the hypoactivated cingulate-cortex neurons following a mild emotional challenge, which again was normalized by environmental enrichment. Paralleling the findings using environmental enrichment, systemic administration of histone-deacetylase-inhibitor MS-275 elicited an anxiolytic-like effect, which was correlated with increased acetylated-histone-3 levels within cingulate-cortex. Finally, as a proof-of-principle, local MS-275 injection into cingulate-cortex rescued enhanced innate anxiety and increased acetylated-histone-3 within the cingulate-cortex, suggesting this epigenetic mark as a biomarker for treatment success.

Conclusions

Taken together, the present findings provide the first causal evidence that the attenuation of high innate anxiety-like behavior via environmental/pharmacological manipulations is epigenetically mediated via acetylation changes within the cingulate-cortex. Finally, histone-3 specific histone-deacetylase-inhibitor could be of therapeutic importance in anxiety disorders.

SUBMITTER: Sah A

PROVIDER: S-EPMC6441131 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.

Sah Anupam A Sotnikov Sergey S Kharitonova Maria M Schmuckermair Claudia C Diepold Rebekka P RP Landgraf Rainer R Whittle Nigel N Singewald Nicolas N

The international journal of neuropsychopharmacology 20190401 4

<h4>Background</h4>Pathological anxiety originates from a complex interplay of genetic predisposition and environmental factors, acting via epigenetic mechanisms. Epigenetic processes that can counteract detrimental genetic risk towards innate high anxiety are not well characterized.<h4>Methods</h4>We used female mouse lines of selectively bred high (HAB)- vs low (LAB)-innate anxiety-related behavior and performed select environmental and pharmacological manipulations to alter anxiety levels as ...[more]

PMID: 30668714

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Dataset Information

Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.

Background

Methods

Results

Conclusions

Publications

Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.

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