ArticleThe international journal of neuropsychopharmacology2019
Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.
Article in The international journal of neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- The role of the anterior cingulate cortex in anxiety control, from circuits to disorders.Frontiers in psychiatry · 2026Review
- Article
- Less is more: calorie restriction as a therapeutic for mental health disorders.Frontiers in psychiatry · 2025Review
- Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice.Frontiers in pharmacology · 2024Article
- Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.Current neuropharmacology · 2024Article
- The role of epigenetics in anxiety disorders.Molecular biology reports · 2023Review
- New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics.Journal of gastroenterology · 2023Review
- Review
- The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review.eNeuro · 2023Review
- Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events.International journal of molecular sciences · 2022Article
- Mitochondrial brain proteome acetylation levels and behavioural responsiveness to amphetamine are altered in mice lacking Sirt3.Frontiers in physiology · 2022Article
- NRM 2021 Abstract Booklet.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Neuroinflammatory alterations in trait anxiety: modulatory effects of minocycline.Translational psychiatry · 2020Article
- Anxious Behavior of Adult CD1 Mice Perinatally Exposed to Low Concentrations of Ethanol Correlates With Morphological Changes in Cingulate Cortex and Amygdala.Frontiers in behavioral neuroscience · 2020Article
- The Potential Role of Epigenetic Drugs in the Treatment of Anxiety Disorders.Neuropsychiatric disease and treatment · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPathological 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.
methodsWe 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.
resultsInborn 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.
conclusionsTaken 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.