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Neural Plasticity
Volume 2016 (2016), Article ID 6752193, 14 pages
Review Article

Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies

1Laboratorio di Neuropsicofarmacologia e Neurogenomica Funzionale, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Università degli Studi di Milano, 20133 Milano, Italy
2Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA

Received 1 December 2015; Accepted 17 February 2016

Academic Editor: Menahem Segal

Copyright © 2016 Laura Musazzi and Jordan Marrocco. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli.