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Lo Iacono L.,IRCSS Fondazione Santa Lucia Rome Italy | Valzania A.,IRCSS Fondazione Santa Lucia Rome Italy | Visco-Comandini F.,University College London | Arico E.,Oncology and Molecular Medicine Istituto Superiore di Sanita | And 8 more authors.
Addiction Biology | Year: 2016

Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaine-seeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals. © 2016 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. Source


Felli N.,Oncology and Molecular Medicine Istituto Superiore di Sanita | Cianetti L.,Oncology and Molecular Medicine Istituto Superiore di Sanita | Pelosi E.,Oncology and Molecular Medicine Istituto Superiore di Sanita | Care A.,Oncology and Molecular Medicine Istituto Superiore di Sanita | And 6 more authors.
BMC Systems Biology | Year: 2010

Background: The differentiation process, proceeding from stem cells towards the different committed cell types, can be considered as a trajectory towards an attractor of a dynamical process. This view, taking into consideration the transcriptome and miRNome dynamics considered as a whole, instead of looking at few 'master genes' driving the system, offers a novel perspective on this phenomenon. We investigated the 'differentiation trajectories' of the hematopoietic system considering a genome-wide scenario.Results: We developed serum-free liquid suspension unilineage cultures of cord blood (CB) CD34+hematopoietic progenitor cells through erythroid (E), megakaryocytic (MK), granulocytic (G) and monocytic (Mo) pathways. These cultures recapitulate physiological hematopoiesis, allowing the analysis of almost pure unilineage precursors starting from initial differentiation of HPCs until terminal maturation. By analyzing the expression profile of protein coding genes and microRNAs in unilineage CB E, MK, G and Mo cultures, at sequential stages of differentiation and maturation, we observed a coordinated, fully interconnected and scalable character of cell population behaviour in both transcriptome and miRNome spaces reminiscent of an attractor-like dynamics. MiRNome and transcriptome space differed for a still not terminally committed behaviour of microRNAs.Conclusions: Consistent with their roles, the transcriptome system can be considered as the state space of a cell population, while the continuously evolving miRNA space corresponds to the tuning system necessary to reach the attractor. The behaviour of miRNA machinery could be of great relevance not only for the promise of reversing the differentiated state but even for tumor biology. © 2010 Felli et al; licensee BioMed Central Ltd. Source

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