Nickel, a known occupational/environmental hazard, may cross the placenta and reach appreciable concentrations in various fetal organs, including the brain. The aim of this study was to investigate whether nickel interferes with the process of neuronal differentiation. Following a 4 week treatment with retinoic acid (10 μM), the human teratocarcinoma-derived NTera2/D1 cell line (NT2 cells) terminally differentiate into neurons which recapitulate many features of human fetal neurons. The continuous exposure of the differentiating NT2 cells to a not cytotoxic nickel concentration (10 μM) increased the expression of specific neuronal differentiation markers such as Neural Cell Adhesion Molecule (NCAM) and Microtubule Associated Protein 2 (MAP2). Furthermore, nickel exposure increased the expression of Hypoxia-Inducible-Factor-1α (HIF-1α) and induced the activation of the AKT/PKB kinase pathway, as shown by the increase of P(Ser-9)-GSK-3β, the inactive form of glycogen synthase kinase-3β (GSK-3β). Intriguingly, by the end of the fourth week the expression of tyrosine hydroxylase (TH) protein, a marker of dopaminergic neurons, was lower in nickel-treated than in control cultures. Thus, likely by partially mimicking hypoxic conditions, a not-cytotoxic nickel concentration appears to alter the process of neuronal differentiation and hinder the expression of the dopaminergic neuronal phenotype. Taken together, these results suggest that nickel, by altering normal brain development, may increase susceptibility to neuro-psychopathology later in life.

Ceci, C., Barbaccia, M.l., Pistritto, G. (2015). A not cytotoxic nickel concentration alters the expression of neuronal differentiation markers in NT2 cells. NEUROTOXICOLOGY, 47, 47-53 [10.1016/j.neuro.2015.01.001].

A not cytotoxic nickel concentration alters the expression of neuronal differentiation markers in NT2 cells

Ceci, C;BARBACCIA, MARIA LUISA;PISTRITTO, GIUSEPPA
2015-01-19

Abstract

Nickel, a known occupational/environmental hazard, may cross the placenta and reach appreciable concentrations in various fetal organs, including the brain. The aim of this study was to investigate whether nickel interferes with the process of neuronal differentiation. Following a 4 week treatment with retinoic acid (10 μM), the human teratocarcinoma-derived NTera2/D1 cell line (NT2 cells) terminally differentiate into neurons which recapitulate many features of human fetal neurons. The continuous exposure of the differentiating NT2 cells to a not cytotoxic nickel concentration (10 μM) increased the expression of specific neuronal differentiation markers such as Neural Cell Adhesion Molecule (NCAM) and Microtubule Associated Protein 2 (MAP2). Furthermore, nickel exposure increased the expression of Hypoxia-Inducible-Factor-1α (HIF-1α) and induced the activation of the AKT/PKB kinase pathway, as shown by the increase of P(Ser-9)-GSK-3β, the inactive form of glycogen synthase kinase-3β (GSK-3β). Intriguingly, by the end of the fourth week the expression of tyrosine hydroxylase (TH) protein, a marker of dopaminergic neurons, was lower in nickel-treated than in control cultures. Thus, likely by partially mimicking hypoxic conditions, a not-cytotoxic nickel concentration appears to alter the process of neuronal differentiation and hinder the expression of the dopaminergic neuronal phenotype. Taken together, these results suggest that nickel, by altering normal brain development, may increase susceptibility to neuro-psychopathology later in life.
19-gen-2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
microtubule-associated-protein2/MAP2; neural cell adhesion molecule/NCAM; hypoxia-inducible-factor-1α/HIF-1α; glycogen synthase kinase/GSK-3β; tyrosine hydroxylase/TH.
Ceci, C., Barbaccia, M.l., Pistritto, G. (2015). A not cytotoxic nickel concentration alters the expression of neuronal differentiation markers in NT2 cells. NEUROTOXICOLOGY, 47, 47-53 [10.1016/j.neuro.2015.01.001].
Ceci, C; Barbaccia, Ml; Pistritto, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/108089
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