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dc.date.accessioned2019-11-28T14:33:40Z
dc.date.available2019-11-28T14:33:40Z
dc.date.created2018-04-04T09:19:15Z
dc.date.issued2018
dc.identifier.citationStahl, Katja Rahmani, Soulmaz Prydz, Agnete Skauli, Nadia MacAulay, Nanna Mylonakou, Maria-Niki Torp, Reidun Skare, Øivind Berg, Torill Leergaard, Trygve Brauns Paulsen, Ragnhild Elisabeth Ottersen, Ole Petter Amiry-Moghaddam, Mahmood . Targeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinson's disease. PLoS ONE. 2018, 13(3)
dc.identifier.urihttp://hdl.handle.net/10852/71046
dc.description.abstractMore than 90% of the cases of Parkinson's disease have unknown etiology. Gradual loss of dopaminergic neurons of substantia nigra is the main cause of morbidity in this disease. External factors such as environmental toxins are believed to play a role in the cell loss, although the cause of the selective vulnerability of dopaminergic neurons remains unknown. We have previously shown that aquaglyceroporin AQP9 is expressed in dopaminergic neurons and astrocytes of rodent brain. AQP9 is permeable to a broad spectrum of substrates including purines, pyrimidines, and lactate, in addition to water and glycerol. Here we test our hypothesis that AQP9 serves as an influx route for exogenous toxins and, hence, may contribute to the selective vulnerability of nigral dopaminergic (tyrosine hydroxylase-positive) neurons. Using Xenopus oocytes injected with Aqp9 cRNA, we show that AQP9 is permeable to the parkinsonogenic toxin 1-methyl-4-phenylpyridinium (MPP+). Stable expression of AQP9 in HEK cells increases their vulnerability to MPP+ and to arseniteÐ another parkinsonogenic toxin. Conversely, targeted deletion of Aqp9 in mice protects nigral dopaminergic neurons against MPP+ toxicity. A protective effect of Aqp9 deletion was demonstrated in organotypic slice cultures of mouse midbrain exposed to MPP+ in vitro and in mice subjected to intrastriatal injections of MPP+ in vivo. Seven days after intrastriatal MPP+ injections, the population of tyrosine hydroxylase-positive cells in substantia nigra is reduced by 48% in Aqp9 knockout mice compared with 67% in WT littermates. Our results show that AQP9 ±selectively expressed in catecholaminergic neuronsÐis permeable to MPP+ and suggest that this aquaglyceroporin contributes to the selective vulnerability of nigral dopaminergic neurons by providing an entry route for parkinsonogenic toxins. To our knowledge this is the first evidence implicating a toxin permeable membrane channel in the pathophysiology of Parkinson's disease.
dc.languageEN
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleTargeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinson's disease
dc.typeJournal article
dc.creator.authorStahl, Katja
dc.creator.authorRahmani, Soulmaz
dc.creator.authorPrydz, Agnete
dc.creator.authorSkauli, Nadia
dc.creator.authorMacAulay, Nanna
dc.creator.authorMylonakou, Maria-Niki
dc.creator.authorTorp, Reidun
dc.creator.authorSkare, Øivind
dc.creator.authorBerg, Torill
dc.creator.authorLeergaard, Trygve Brauns
dc.creator.authorPaulsen, Ragnhild Elisabeth
dc.creator.authorOttersen, Ole Petter
dc.creator.authorAmiry-Moghaddam, Mahmood
cristin.unitcode185,51,12,30
cristin.unitnameSeksjon for anatomi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1577130
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS ONE&rft.volume=13&rft.spage=&rft.date=2018
dc.identifier.jtitlePLoS ONE
dc.identifier.volume13
dc.identifier.issue3
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0194896
dc.identifier.urnURN:NBN:no-74168
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn1932-6203
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/71046/1/journal.pone.0194896.pdf
dc.type.versionPublishedVersion
cristin.articleide0194896


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