• Livio Provenzi

DNA methylation in action: From early life exposure to brain growth and behavioral development

How early experiences in our life are able to contribute to the human being we are going to be?

One of the most relevant questions human beings have long-lasting asked to themselves is: "How early experiences in our life are able to contribute to the human being we are going to be?". Recent research in the field of behavioral epigenetics is starting to provide new insights on this issue. The epigenetic regulation of DNA functioning has been shown to be highly susceptible to precocious stressful experiences [1,2]. This is mainly due to a process known as DNA methylation, which acts as a biochemical switch of DNA transcriptional activity: high stress results in high methylation, which means reduced DNA transcription [3]. Very preterm birth and the subsequent hospitalization of infants in the Neonatal Intensive Care Unit (NICU) represent one of the most common early stressful experiences in human beings. During the NICU stay, very preterm infants are exposed to frequent painful and invasive procedures, such as skin-breaking procedures and mechanical ventilation [4]. We have previously showed that NICU-related stress might result in birth-to-discharge increased DNA methylation in stress-related genes of very preterm infants [5] and that this epigenetic regulation is associated with socio-emotional and behavioral outcomes at 3 months [6,7].

Integrating environment, brain, epigenetics and behavior provides unique insights on the "full movie" of early life contribution to our developmental trajectories

Unfortunately, the access to epigenetic regulation in humans is restricted to peripheral tissues whereas information on epigenetic status and the relative transcriptome can be observed directly in the brain in animal models. Still, integrating environment, brain, epigenetics and behavior provides unique insights on the "full movie" of early life contribution to our developmental trajectories. In this 2018 paper from our lab in collaboration with the NICU of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan [8], we documented that NICU-related birth-to-discharge increase in the serotonin transporter gene (i.e., SLC6A4) gene methylation was associated with reduced bilateral brain volumes of the anterior temporal lobes at term equivalent age in very preterm infants. Moreover, reduced brain volume of anterior temporal lobes was further predictive of socio-emotional development at 12 months (corrected age for prematurity). These findings depict a preliminary scenario of a longitudinal and perspective pathway starting from early exposure to a stressful environment (i.e., NICU), which affects epigenetic regulation of a stress-related gene (i.e., SLC6A4), further impacting on brain growth at term equivalent age (i.e., anterior temporal lobes volume) and predicting the long-term developmental outcome (i.e., socio-emotional functioning).

We are working hard to further integrate risk and protective factors in our behavioral epigenetics studies

So, what's next? The field of behavioral epigenetics is still at its beginning and findings should be considered preliminary. Many other processes might be involved, other than DNA methylation, as well as many other life events - for bad and for good - might be involved in epigenetic regulation and contribute to our developmental trajectories. As such, at the 0-3 Centre for the at-Risk Infant, we are working hard to further integrate risk and protective factors in our behavioral epigenetics studies. To this extent, we have opened a call for papers through a Research Topic in Frontiers in Developmental Psychology and Frontiers in Behavioral Neuroscience asking international colleagues to provide original data, viewpoints and methodological insights to further advance the field by focusing on the complex interconnections among risk factors, protective care and epigenetics in human development.


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Keywords: #epigenetics; #methylation; #stress; #preterminfants; #brain; #development


Article citation: Fumagalli M, Provenzi L, De Carli P et al (2018) From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth. Plos One, 13(1): e0190602. https://doi.org/10.1371/journal.pone.0190602

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