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.

Zebrafish as a systems toxicology model for developmental neurotoxicity testing

“…Reduced mbp expression has also been reported in rats perinatally exposed to polychlorinated biphenyl (Campagna et al. ).…”

“…They found that the expression of mbp but not gfap was significantly decreased in the offspring compared with that in the control offspring. Reduced mbp expression has also been reported in rats perinatally exposed to polychlorinated biphenyl (Campagna et al 2011). A major challenge for DNT is the lack of knowledge of the molecular targets of potential neurotoxicants that results in activation of toxicity pathways and ultimately results in abnormal development .…”

New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of coenzyme q10 in abating the detrimental outcomes

“…The neurological impact of PCBs have been comprehensively studied in various animal models of PCB exposure, either as single congeners or mixtures, during different periods of the animal's lifespan [9]. Many of these studies were conducted only on young animals or animals exposed prenatally to PCBs [10,11]. However, a study conducted on adult rats found that spatial learning behavior was altered due to PCB exposure, thereby indicating that PCBs can alter the nervous system in adult animals as well [12,13].…”

Proteomics as a tool to gain more insight into sub-lethal toxicological effects

“…Ionexchange and reversed-phase chromatography were found helpful, as well as different affinity chromatography steps (e.g., group-specific enrichment for phosphoproteins; Thingholm et al, 2009). Chromatographic separation of peptide mixtures may also be a versatile step to facilitate protein identification in approaches involving a one-dimensional SDS-PAGE step (Sarioglu et al, 2006;Campagna et al, 2011;Brunelli et al, 2012), when proteins with major abundance tend to mask minor protein components.…”

“…For obtaining quantitative results, they require absolute reproducibility in the peptide separation and a high number of technical replicates, to ensure statistical relevance to the obtained results. In a semiquantitative approach, label-free MS was applied to study the influence of PCB138 on fetal brain proteins (Campagna et al, 2011).…”