Universität zu Köln

Pistollato, Francesca, Louisse, Jochem ORCID: 0000-0002-0517-2288, Scelfo, Bibiana ORCID: 0000-0002-2261-8683, Mennecozzi, Milena, Accordi, Benedetta, Basso, Giuseppe, Gaspar, John Antonydas, Zagoura, Dimitra, Barilari, Manuela, Palosaari, Taina, Sachinidis, Agapios and Bremer-Hoffmann, Susanne (2014). Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: Effects of CREB pathway inhibition. Toxicol. Appl. Pharmacol., 280 (2). S. 378 - 389. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1096-0333

Full text not available from this repository.

Abstract

According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer a unique opportunity to derive physiologically relevant human cell types to measure molecular and cellular effects of such pathway modulations. Here we compared the neuronal differentiation propensity of hESCs and hiPSCs with the aim to develop novel hiPSC-based tools for measuring pathway perturbation in relation to molecular and cellular effects in vitro. Among other fundamental pathways, also, the cAMP responsive element binding protein (CREB) pathway was activated in our neuronal models and gave us the opportunity to study time-dependent effects elicited by chemical perturbations of the CREB pathway in relation to cellular effects. We show that the inhibition of the CREB pathway, using 2-naphthol-AS-E-phosphate (KG-501), induced an inhibition of neurite outgrowth and synaptogenesis, as well as a decrease of MAP2(+) neuronal cells. These data indicate that a CREB pathway inhibition can be related to molecular and cellular effects that may be relevant for neurotoxicity testing, and, thus, qualify the use of our hiPSC-derived neuronal model for studying chemical-induced neurotoxicity resulting from pathway perturbations. (C) 2014 The Authors. Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pistollato, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Louisse, Jochem UNSPECIFIED orcid.org/0000-0002-0517-2288 UNSPECIFIED Scelfo, Bibiana UNSPECIFIED orcid.org/0000-0002-2261-8683 UNSPECIFIED Mennecozzi, Milena UNSPECIFIED UNSPECIFIED UNSPECIFIED Accordi, Benedetta UNSPECIFIED UNSPECIFIED UNSPECIFIED Basso, Giuseppe UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaspar, John Antonydas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zagoura, Dimitra UNSPECIFIED UNSPECIFIED UNSPECIFIED Barilari, Manuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Palosaari, Taina UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Bremer-Hoffmann, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-425733
DOI:	10.1016/j.taap.2014.08.007
Journal or Publication Title:	Toxicol. Appl. Pharmacol.
Volume:	280
Number:	2
Page Range:	S. 378 - 389
Date:	2014
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1096-0333
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language C-FOS; RESPONSE ELEMENT; X-INACTIVATION; MECHANISMS; EXPRESSION; TOXICITY; DIFFERENTIATION; IDENTIFICATION; CONTRIBUTES; ARRAY Multiple languages Pharmacology & Pharmacy; Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42573