Abstract
Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA (alteration of maternal care) on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced additional hits. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naïve, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.
Highlights
Synaptic connections in the brain are continuously altered, including via gene expression, to accommodate experiences, thereby preparing the organism to deal with future events [1,2,3]
We synthesized the evidence of 39 publications investigating the effects of Early-life adversity (ELA) on Immediate-early genes (IEGs) expression in mice and rats
In order to circumvent this limitation, we systematically reviewed the available literature on several IEGs in males and females
Summary
Synaptic connections in the brain are continuously altered, including via gene expression, to accommodate experiences, thereby preparing the organism to deal with future events [1,2,3] This potential for adaptation, called neuronal or synaptic plasticity, is prominently present during critical periods early in life [4]. For this reason, adverse experiences throughout childhood–such as physical, sexual or emotional abuse–have far-reaching effects on an individual’s brain function and structure, and on cognition and behavior [5,6,7]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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