title: Cerebellum proteomics addressing the cognitive deficit of rats perinatally exposed to the food-relevant polychlorinated biphenyl 138.
abstract: Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in humans and laboratory animals by mechanisms that remain unknown. Recently, it has been shown that developmental exposure to 2,2',3,4,4',5'-hexachlorobiphenyl (PCB138), a food-relevant PCB congener, decreases the learning ability of young rats. The aim of this study was to characterize the effect of perinatal exposure to PCB138 on the brain proteome profile in young rats in order to gain insight into the mechanisms underlying PCB138 neurotoxicity. Comparison of the cerebellum proteome from 3-month-old unexposed and PCB138-exposed male offspring was performed using state-of-the-art label-free semiquantitative mass spectrometry method. Biological pathways associated with Ca(2+) homeostasis and androgen receptor signaling pathways were primarily disrupted. These perturbations may contribute toward a premature ageing-like proteome profile of the cerebellum that is triggered by PCB138 exposure in males. Our proteomic data provide insights into the phenomena that may be contributing to the PCB138 neurotoxicity effects observed in laboratory rodents and correlate with PCB exposure and decreased cognitive functions in humans. As such, this study highlights the importance of PCB138 as a risk factor in developmental neurotoxicity in laboratory rodents and humans.
authors.affiliation: Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milano, Italy. roberta.pastorelli@marionegri.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Campagna
authors.forename: Laura
authors.initials: L
authors.lastname: Brunelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Airoldi
authors.forename: Roberto
authors.initials: R
authors.lastname: Fanelli
authors.forename: Helen
authors.initials: H
authors.lastname: Hakansson
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Heimeier
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
authors.forename: Jordi
authors.initials: J
authors.lastname: Boix
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: Pastorelli
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005506:Food Contamination; D008297:Male; D018811:Maternal Exposure; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D004785:Environmental Pollutants; D011506:Proteins; C029790:2,2',3',4,4',5-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls