Toxics 2014, 2(3), 443-463; doi:10.3390/toxics2030443
Article

Changes in miRNA Expression Profiling during Neuronal Differentiation and Methyl Mercury-Induced Toxicity in Human in Vitro Models

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Received: 4 June 2014; in revised form: 31 July 2014 / Accepted: 5 August 2014 / Published: 29 August 2014
(This article belongs to the Special Issue Developmental Neurotoxicology)
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.
Abstract: MicroRNAs (miRNAs) are implicated in the epigenetic regulation of several brain developmental processes, such as neurogenesis, neuronal differentiation, neurite outgrowth, and synaptic plasticity. The main aim of this study was to evaluate whether miRNA expression profiling could be a useful approach to detect in vitro developmental neurotoxicity. For this purpose, we assessed the changes in miRNA expression caused by methyl mercury chloride (MeHgCl), a well-known developmental neurotoxicant, comparing carcinoma pluripotent stem cells (NT-2) with human embryonic stem cells (H9), both analyzed during the early stage of neural progenitor commitment into neuronal lineage. The data indicate the activation of two distinct miRNA signatures, one activated upon neuronal differentiation and another upon MeHgCl-induced toxicity. Particularly, exposure to MeHgCl elicited, in both neural models, the down-regulation of the same six out of the ten most up-regulated neuronal pathways, as shown by the up-regulation of the corresponding miRNAs and further assessment of gene ontology (GO) term and pathway enrichment analysis. Importantly, some of these common miRNA-targeted pathways defined in both cell lines are known to play a role in critical developmental processes, specific for neuronal differentiation, such as axon guidance and neurotrophin-regulated signaling. The obtained results indicate that miRNAs expression profiling could be a promising tool to assess developmental neurotoxicity pathway perturbation, contributing towards improved predictive human toxicity testing.
Keywords: miRNAs expression profiling; NT-2 and H9 cell lines; neuronal cultures; pathways of toxicity
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MDPI and ACS Style

Pallocca, G.; Fabbri, M.; Nerini-Molteni, S.; Pistollato, F.; Zagoura, D.; Sacco, M.G.; Gribaldo, L.; Bremer-Hoffmann, S.; Bal-Price, A. Changes in miRNA Expression Profiling during Neuronal Differentiation and Methyl Mercury-Induced Toxicity in Human in Vitro Models. Toxics 2014, 2, 443-463.

AMA Style

Pallocca G, Fabbri M, Nerini-Molteni S, Pistollato F, Zagoura D, Sacco MG, Gribaldo L, Bremer-Hoffmann S, Bal-Price A. Changes in miRNA Expression Profiling during Neuronal Differentiation and Methyl Mercury-Induced Toxicity in Human in Vitro Models. Toxics. 2014; 2(3):443-463.

Chicago/Turabian Style

Pallocca, Giorgia; Fabbri, Marco; Nerini-Molteni, Silvia; Pistollato, Francesca; Zagoura, Dimitra; Sacco, Maria G.; Gribaldo, Laura; Bremer-Hoffmann, Susanne; Bal-Price, Anna. 2014. "Changes in miRNA Expression Profiling during Neuronal Differentiation and Methyl Mercury-Induced Toxicity in Human in Vitro Models." Toxics 2, no. 3: 443-463.

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