English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior

Sah, A., Sotnikov, S., Kharitonova, M., Schmuckermair, C., Diepold, R. P., Landgraf, R., et al. (2019). Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior. International Journal of Neuropsychopharmacology, 22(4), 317-328. doi:10.1093/ijnp/pyz004.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Sah, Anupam, Author
Sotnikov, Sergey1, Author           
Kharitonova, Maria, Author
Schmuckermair, Claudia, Author
Diepold, Rebekka P.1, Author           
Landgraf, Rainer1, Author           
Whittle, Nigel, Author
Singewald, Nicolas, Author
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

Content

show
hide
Free keywords: -
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2019-01-212019
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000467778800007
DOI: 10.1093/ijnp/pyz004
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: International Journal of Neuropsychopharmacology
  Other : Int. J. Neuropsychopharmacol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Cambridge : Cambridge University Press
Pages: - Volume / Issue: 22 (4) Sequence Number: - Start / End Page: 317 - 328 Identifier: ISSN: 1461-1457
CoNE: https://pure.mpg.de/cone/journals/resource/963017835281