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Title: Synaptic contacts impaired by styrene-7,8-oxide toxicity

Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration ofmore » neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [2]
  1. Dip. di Farmacologia e Fisiologia Umana, Facolta di Medicina e Chirurgia, Universita degli Studi di Bari, 70124 Italy (Italy), E-mail: pcorsi@fisiol.uniba.it
  2. Dip. di Medicina Interna e Pubblica, Facolta di Medicina e Chirurgia, Universita di Bari (Italy)
  3. Dip. di Anatomia Umana e Istologia, Facolta di Medicina e Chirurgia, Universita di Bari (Italy)
  4. Dip. di Anatomia, Farmacologia e Scienze Medico Forensi, Facolta di Medicina e Chirurgia, Universita di Parma (Italy)
Publication Date:
OSTI Identifier:
21077812
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 224; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.06.021; PII: S0041-008X(07)00280-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; DOPAMINE; DOSES; MICROTUBULES; NERVE CELLS; OXIDES; OXYGEN; PROTEINS; STYRENE; TOXICITY