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Impact of early-life stress on the medial prefrontal cortex functions – a search for the pathomechanisms of anxiety and mood disorders
Abstract
Although anxiety and mood disorders (MDs) are the most common mental diseases, the etiologies and mechanisms of these psychopathologies are still a matter of debate. The medial prefrontal cortex (mPFC) is a brain structure that is strongly implicated in the pathophysiology of these disorders. A growing number of epidemiological and clinical studies show that early-life stress (ELS) during the critical period of brain development may increase the risk for anxiety and MDs. Neuroimaging analyses in humans and numerous reports from animal models clearly demonstrate that ELS affects behaviors that are dependent on the mPFC, as well as neuronal activity and synaptic plasticity within the mPFC. The mechanisms engaged in ELS-induced changes in mPFC function involve alterations in the developmental trajectory of the mPFC and may be responsible for the emergence of both early-onset (during childhood and adolescence) and adulthood-onset anxiety and MDs. ELS-evoked changes in mPFC synaptic plasticity may constitute an example of metaplasticity. ELS may program brain functions by affecting glucocorticoid levels. On the molecular level, ELS-induced programming is registered by epigenetic mechanisms, such as changes in DNA methylation pattern, histone acetylation and microRNA expression. Vulnerability and resilience to ELS-related anxiety and MDs depend on the interaction between individual genetic predispositions, early-life experiences and later-life environment. In conclusion, ELS may co…
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Dnmt3a1 viral overexpression in mouse dorsal mPFC rescued CSDS-induced anxiety.
“Dnmt3a1 viral overexpression in mouse dorsal mPFC, which regulates fear, anxiety, risk taking, and decision-making, rescued CSDS-induced anxiety (Chocyk et al., 2013; Elliott et al., 2016).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Chocyk et al., 2013
The mouse dorsal mPFC regulates fear, anxiety, risk taking, and decision-making.
“mouse dorsal mPFC, which regulates fear, anxiety, risk taking, and decision-making”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Chocyk et al., 2013
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“Moreover, histopathological examinations showed several morphological abnormalities, such as reductions in synapses and synaptic proteins and elimination of glial cells in the mPFC of MD subjects [20].”
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Metadata
- Authors
- Chocyk, A., Majcher-Maślanka, I., Dudys, D., Przyborowska, A., & Wędzony, K.
- Affiliations
- Maj Institute of Pharmacology (PL)
- Corresponding author
- Chocyk, Agnieszka
- ORCID
- Chocyk, Agnieszka
- Venue
- Pharmacological Reports
- Published
- 2013-11
- Volume
- 65
- Issue
- 6
- Pages
- 1462-1470
- ISSN
- 1734-1140 (ISSN-L)
- OpenAlex
- W2025997841
- Cited by
- 55
- References
- 72
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 0.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- EU European Regional Development Fund (Poland) (POIG.01.01.02-12-004/09-00)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- early life stress, medial prefrontal cortex, anxiety disorders, mood disorders, synaptic plasticity, metaplasticity, glucocorticoids, epigenetics, DNA methylation, histone acetylation, microRNA, developmental programming, vulnerability and resilience, animal models of stress
- MeSH terms
- Animals, Anxiety, Humans, Stress, Psychological, Prefrontal Cortex, Mood Disorders, Epigenesis, Genetic
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