title: Epigenetic modifications induced by early enrichment are associated with changes in timing of induction of BDNF expression.
abstract: During early postnatal phase, the environment deeply affects developmental trajectories through epigenetic mechanisms that control the levels of key molecules for brain function, such as neurotrophins. Indeed, it has been shown that adverse early experiences induce epigenetic modifications leading to decreased brain derived neurotrophic factor (BDNF) levels at adulthood. However, no data about the effects of enriching early experiences are available. Here we exploit the mouse Communal Nest (CN) paradigm in order to investigate the effects of a highly stimulating early social environment on BDNF epigenetic modifications and protein expression at adulthood. CN, which consists of a single nest where three mothers keep their pups together and share care-giving behavior until weaning, is characterized by high levels of maternal behavior and peer interactions. Our results show that CN leads to high levels of histone acetylation at the BDNF gene at adulthood, which is more permissive to expression. However, such epigenetic modification is associated to increased BDNF protein expression only 1h after an environmental challenge and not at baseline or 3h after the challenge, suggesting that the epigenetic modifications do not affect expression under steady-state conditions but allow a fast increase in BDNF levels following stimulation. The present findings corroborate the role of epigenetic modifications in mediating the effects of the early social environment on adult brain function and behavior. In addition, these show, for the first time, an association between an epigenetic modification and a change in the rapidity of induction of protein expression, expanding the knowledge on the mechanisms by which epigenetic changes modify brain function.
authors.affiliation: Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy. igor.branchi@iss.it
authors.forename: Igor
authors.initials: I
authors.lastname: Branchi
authors.forename: Nina N
authors.initials: NN
authors.lastname: Karpova
authors.forename: Ivana
authors.initials: I
authors.lastname: D'Andrea
authors.forename: Eero
authors.initials: E
authors.lastname: Castrén
authors.forename: Enrico
authors.initials: E
authors.lastname: Alleva
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D057890:Epigenomics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012931:Social Environment; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006657:Histones