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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

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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. Agrowing 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 DNAmethylation 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 constitute a significant etiological factor for anxiety and MDs, whereas animal models of ELS are helpful tools for understanding the pathomechanisms of these disorders.

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Abbreviations

11B-HSD2:

11β-hydroxysteroid dehydrogenase type 2

BDNF:

brain-derived neurotrophic factor

ELS:

early-life stress

GDNF:

glial cell-derived neurotrophic factor

GFAP:

glial fibrillary acidic protein

GR:

glucocorticoid receptor

ILC:

infralimbic cortex

LTD:

long-term depression

LTP:

long-term potentiation

MDs:

mood disorders

miRNA:

microRNA

mPFC:

medial prefrontal cortex

MS:

maternal separation

NCAM:

neural cell adhesion molecules

PLC:

prelimbic cortex

PTSD:

post-traumatic stress disorder

SHRP:

stress hyporesponsive period

vmPFC:

ventromedial prefrontal cortex

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  1. Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Smętna 12, PL 31-343, Poland

    Agnieszka Chocyk, Iwona Majcher-Maślanka, Dorota Dudys, Aleksandra Przyborowska & Krzysztof Wędzony

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  1. Agnieszka Chocyk
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Chocyk, A., Majcher-Maślanka, I., Dudys, D. et al. Impact of early-life stress on the medial prefrontal cortex functions — a search for the pathomechanisms of anxiety and mood disorders. Pharmacol. Rep 65, 1462–1470 (2013). https://doi.org/10.1016/S1734-1140(13)71506-8

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