title: Insight into the neuroproteomics effects of the food-contaminant non-dioxin like polychlorinated biphenyls.
abstract: Recent studies showed that food-contaminant non-dioxin-like polychlorinated biphenyls (NDL-PCBs) congeners (PCB52, PCB138, PCB180) have neurotoxic potential, but the cellular and molecular mechanisms underlying neuronal damage are not entirely known. The aim of this study was to assess whether in-vitro exposure to NDL-PCBs may alter the proteome profile of primary cerebellar neurons in order to expand our knowledge on NDL-PCBs neurotoxicity. Comparison of proteome from unexposed and exposed rat cerebellar neurons was performed using state-of-the-art label-free semi-quantitative mass-spectrometry method. We observed significant changes in the abundance of several proteins, that fall into two main classes: (i) novel targets for both PCB138 and 180, mediating the dysregulation of CREB pathways and ubiquitin-proteasome system; (ii) different congeners-specific targets (alpha-actinin-1 for PCB138; microtubule-associated-protein-2 for PCB180) that might lead to similar deleterious consequences on neurons cytoskeleton organization. Interference of the PCB congeners with synaptic formation was supported by the increased expression of pre- and post-synaptic proteins quantified by western blot and immunocytochemistry. Expression alteration of synaptic markers was confirmed in the cerebellum of rats developmentally exposed to these congeners, suggesting an adaptive response to neurodevelopmental toxicity on brain structures. As such, our work is expected to lead to new insights into the mechanisms of NDL-PCBs neurotoxicity.
authors.affiliation: Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brunelli
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.forename: Roberta
authors.initials: R
authors.lastname: Campagna
authors.forename: Luisa
authors.initials: L
authors.lastname: Airoldi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: De Paola
authors.forename: Roberto
authors.initials: R
authors.lastname: Fanelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mariani
authors.forename: Marco
authors.initials: M
authors.lastname: Mazzoletti
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004147:Dioxins / Q000737:chemistry / Q000633:toxicity; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity; D005506:Food Contamination; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D020543:Proteome / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004147:Dioxins; D004785:Environmental Pollutants; D009419:Nerve Tissue Proteins; D020543:Proteome; D011078:Polychlorinated Biphenyls