ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Science 2018;359:1395-1399

Brain development and behavior are influenced by early life experiences, such as nutrients, stress, adversity and maternal care. While we believe the epigenome is the mediator, these authors investigated whether the genome itself of individual brain cells could be changed by environmental factors. A possible mechanism relies on mobile DNA sequences that change their position within the genome by a DNA-based (transposition) or RNA-based (retrotransposition) mechanism. They show that pups subjected to low maternal care or maternal separation for the first 2 weeks accumulated LINE-1 retrotransposons specifically in the hippocampus, known for its plasticity, but not in the frontal cortex - a somatic mosaic event.

The generation of genomic diversity by LINE-1 elements is a dynamic, lifelong process that begins during embryonic development. Retrotransposition activity is increased as neural progenitors differentiate into neurons. When the brain undergoes extensive growth and differentiation in early life, it uncovers the sensitivity of LINE-1 to experiences. LINE-1 retrotransposition rates are higher in the mouse brain compared with other tissues, and more so in the hippocampus, a region sensitive to environmental stimuli. During the first week of life, the hippocampus still undergoes extensive cell division and differentiation, and fosters retrotransposition. These results indicate that plasticity occurs at the level of the DNA sequence in response to environmental perturbations. Similar changes in the human hippocampus, where emotions are formed and processed may account for the imprinting of environmental cues around age 1-year (the equivalent of the mouse’s 2^nd week) on reproductive (sexual) function later in life.