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dc.date.accessioned2013-03-12T08:46:28Z
dc.date.available2016-01-26T23:30:16Z
dc.date.issued2010en_US
dc.date.submitted2011-01-18en_US
dc.identifier.citationBerntsen, Hanne Friis. Neurotoxic effects on cerebellar granule cells and induction of ROS formation in human neutrophil granulocytes after exposure to polychlorinated biphenyls and penitrem A. Masteroppgave, University of Oslo, 2010en_US
dc.identifier.urihttp://hdl.handle.net/10852/11804
dc.description.abstractPolychlorinated biphenyls (PCBs) are persistant organic pollutants that bioaccumulate and biomagnify through the food chain. Exposure to ortho-chlorinated PCBs has been associated with effects on the nervous and immune systems. Penitrem A is a mycotoxin found to cause neurological symptoms in dogs after ingestion of mouldy food. There have also been cases of suspected penitrem A intoxication in humans. The aim of this study was to investigate differences in neurotoxicity in cerebellar granule cells between low and highly chlorinated ortho-substituted PCBs in vitro, and mechanisms underlying their toxicity. The neurotoxic potential of penitrem A was also investigated. Furthermore, the ability of different PCB congeners and of penitrem A to induce ROS production was investigated in human neutrophil granulocytes in vitro. Cerebellar granule cells were exposed to low and highly chlorinated PCBs, as well as to penitrem A. Effects of potentially neuroprotective substances was also assessed after exposure to the toxic substances. The MTT assay was used to assess cell survival. Human neutrophil granulocytes were also exposed to low and highly chlorinated PCBs and penitrem A. ROS production after exposure was assessed with the DCF and luminol chemiluminescence assays. Effects of inhibitors of ROS production was assessed to identify potential pathways involved in the ROS production. In this study, the higher chlorinated PCBs were more toxic to cerebellar granule cells in vitro than lower chlorinated congeners. Cytoprotective effects were found for the substances vitamin E and MK-801. This may indicate involvement of ROS production and NMDA receptors in PCB neurotoxicity. The lower chlorinated PCBs induced more ROS production in human neutrophil granulocytes than the higher chlorinated congeners. Co-incubation with the substances U0126, BAPTA-AM, vitamin E, SP600125, SB203580, FK-506 and CsA significantly reduced ROS levels. The mycotoxin penitrem A caused more cell death in cerebellar granule cells with increasing concentration and exposure time, and increasing concentrations also induced a dose dependent increase in ROS production in human neutrophil granulocytes. Co-incubation with GABA, phenobarbital, diazepam, vitamin E, BAPTA-AM, SP600125, FK-506 and cyclosporine A all reduced granule cell death. This may indicate that the GABA receptor, ROS production, disruption of calcium homeostasis and activation of the pro-apoptotic JNK pathway are involved in penitrem A neurotoxicity. U0126, SP600125, SB203580, FK-506, cyclosporine A, vitamin E and BAPTA-AM all reduced ROS production in granulocytes after penitrem A exposure. This may point to an involvement of the MEK 1/2, MEK 5, p38 and JNK pathways in the mechanism of penitrem A-induced ROS production.eng
dc.language.isoengen_US
dc.titleNeurotoxic effects on cerebellar granule cells and induction of ROS formation in human neutrophil granulocytes after exposure to polychlorinated biphenyls and penitrem Aen_US
dc.typeMaster thesisen_US
dc.date.updated2011-11-25en_US
dc.creator.authorBerntsen, Hanne Friisen_US
dc.subject.nsiVDP::489en_US
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Berntsen, Hanne Friis&rft.title=Neurotoxic effects on cerebellar granule cells and induction of ROS formation in human neutrophil granulocytes after exposure to polychlorinated biphenyls and penitrem A&rft.inst=University of Oslo&rft.date=2010&rft.degree=Masteroppgaveen_US
dc.identifier.urnURN:NBN:no-26779en_US
dc.type.documentMasteroppgaveen_US
dc.identifier.duo111095en_US
dc.contributor.supervisorFrode Fonnum, Sven Ivar Walaas, Steinar Øvrebøen_US
dc.identifier.bibsys112295061en_US
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/11804/1/Berntsen.pdf


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