Proteomic characterization in the hippocampus of prenatally stressed rats J. Mairesse a , A.S. Vercoutter-Edouart b , J. Marrocco a , A.R. Zuena c , A. Giovine a, c , F. Nicoletti c , d , J.C. Michalski b , S. Maccari a , S. Morley-Fletcher a, ⁎ a Neural Plasticity Team-UMR CNRS/USTL n° 8576 Structural and Functional Glycobiology Unit, North University of Lille, France b Cell Signaling Team-UMR CNRS/USTL n° 8576 Structural and Functional Glycobiology Unit, North University of Lille, France c Dept. of Pharmacology, Sapienza University of Rome, Italy d I.N.M. Neuromed, Pozzilli, Italy ARTICLE INFO ABSTRACT Article history: Received 22 August 2011 Accepted 12 December 2011 Available online 30 December 2011 Rats exposed to early life stress are considered as a valuable model for the study of epigenetic programming leading to mood disorders and anxiety in the adult life. Rats submitted to prenatal restraint stress (PRS) are characterized by an anxious/depressive phenotype associated with neuroadaptive changes in the hippocampus. We used the model of PRS to identify proteins that are specifically affected by early life stress. We therefore performed a proteomic analysis in the hippocampus of adult male PRS rats. We found that PRS induced changes in the expression profile of a number of proteins, involved in the regulation of signal transduction, synaptic vesicles, protein synthesis, cytoskeleton dynamics, and energetic metabolism. Immunoblot analysis showed significant changes in the expression of proteins, such as LASP-1, fascin, and prohibitin, which may lie at the core of the developmental programming triggered by early life stress. © 2011 Elsevier B.V. All rights reserved. Keywords: Proteomics Hippocampus Early life stress Programming Animal model 1. Introduction The low discordance of depression between monozygotic twins and the slow progress in identifying genetic risk factors suggest that epigenetic changes largely contribute to the indi- viduals’ vulnerability to major depressive disorder [1]. Both human and animal studies suggest that exposure to stressful events during critical periods of brain development triggers an epigenetic programming leading to low resilience to stress in the adult life [2–8]. Abnormalities of synaptic transmission and plasticity in the hippocampus represent an integral part of this epigenetic program. For example, early life stress resulting from low maternal care in rodents causes a perma- nent reduction in the length of dendritic branching and the number of dendritic spines associated with an impairment of synaptogenesis and long-term potentiation in the hippo- campus [9–11]. This fits nicely with the clinical evidence that poor parental care can compromise cognitive development [12,13]. Rats exposed to prenatal restraint stress (PRS) develop long-lasting biochemical and behavioral changes that likely reflect the induction of a pathological epigenetic program- ming [14,15], and therefore represent a model that meets the criterium of construct validity because it replicates environ- mental factors implicated in the etiology of depression and other stress-related disorders [1]. Alterations induced by PRS comprise a dysfunction of the hypothalamo-pituitary-adrenal (HPA) axis which is reversed by cross fostering at birth [16],a generalized disorganization of circadian rhythms and the sleep–wake cycle, an age-dependent impairment in spatial JOURNAL OF PROTEOMICS 75 (2012) 1764 – 1770 ⁎ Corresponding author at: North University of Lille, Neuroplasticity Team, CNRS UMR 8576/ UGSF, Structural and Functional Glycobiology Unit, Bât C9, Avenue Mendeleiev, 59655 Villeneuve d'Ascq France. Tel.: + 33 32033 6042; fax: + 33 32043 6555. E-mail address: sara.morley-fletcher@univ-lille1.fr (S. Morley-Fletcher). 1874-3919/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jprot.2011.12.017 Available online at www.sciencedirect.com www.elsevier.com/locate/jprot