title: The consequences of early-life adversity: neurobiological, behavioural and epigenetic adaptations.
abstract: During the perinatal period, the brain is particularly sensitive to remodelling by environmental factors. Adverse early-life experiences, such as stress exposure or suboptimal maternal care, can have long-lasting detrimental consequences for an individual. This phenomenon is often referred to as 'early-life programming' and is associated with an increased risk of disease. Typically, rodents exposed to prenatal stress or postnatal maternal deprivation display enhanced neuroendocrine responses to stress, increased levels of anxiety and depressive-like behaviours, and cognitive impairments. Some of the phenotypes observed in these models of early-life adversity are likely to share common neurobiological mechanisms. For example, there is evidence for impaired glucocorticoid negative-feedback control of the hypothalamic-pituitary-adrenal axis, altered glutamate neurotransmission and reduced hippocampal neurogenesis in both prenatally stressed rats and rats that experienced deficient maternal care. The possible mechanisms through which maternal stress during pregnancy may be transmitted to the offspring are reviewed, with special consideration given to altered maternal behaviour postpartum. We also discuss what is known about the neurobiological and epigenetic mechanisms that underpin early-life programming of the neonatal brain in the first generation and subsequent generations, with a view to abrogating programming effects and potentially identifying new therapeutic targets for the treatment of stress-related disorders and cognitive impairment.
authors.affiliation: LIA, International Laboratory Associated, UMR 8576 CNRS Neural plasticity Team, University of Lille 1, France and Sapienza University of Rome, IRCCS NEUROMED, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Maccari
authors.forename: H J
authors.initials: HJ
authors.lastname: Krugers
authors.forename: S
authors.initials: S
authors.lastname: Morley-Fletcher
authors.forename: M
authors.initials: M
authors.lastname: Szyf
authors.forename: P J
authors.initials: PJ
authors.lastname: Brunton
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000196:embryology / Q000502:physiology; D044127:Epigenesis, Genetic; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System; D010913:Pituitary-Adrenal System; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D013312:Stress, Physiological
chemical_list: D018698:Glutamic Acid
keywords: DNA methylation; HPA axis; cognition; hippocampus; maternal behaviour; mood disorders; prenatal stress