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Sökning: L773:1872 7549 OR L773:0166 4328 > Nasal inoculation w...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003488naa a2200433 4500
001oai:DiVA.org:umu-71313
003SwePub
008130526s2013 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-713132 URI
0247 a https://doi.org/10.1016/j.bbr.2013.01.0112 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Gruden, Marina A.4 aut
2451 0a Nasal inoculation with a-synuclein aggregates evokes rigidity, locomotor deficits and immunity to such misfolded species as well as dopamine
264 1b Elsevier BV,c 2013
338 a print2 rdacarrier
520 a Animal models of Parkinson's disease (PD) have been widely used to investigate the pathogenesis of this neurodegenerative disorder which is typically associated with the specific and largely disordered protein alpha-synuclein (alpha-syn). In the current study, the nasal vector was used to deliver alpha-syn aggregates to the brain. Both alpha-syn oligomers and its fibrils were firstly characterized using atomic force microscopy and the thioflavin T binding assay. The toxic oligomers alone (0.48 mg/kg) or their 50:50 combination with fibrils (in a total dose of 0.48 mg/kg) were then given intranasally for ten days in mice and PD-mimetic symptoms as well as humoral immunity to these species and dopamine (DA) were evaluated simultaneously. Open-field behavioral deficits indicated by rigidity and reduced locomotor activity were induced by the dual administration of alpha-syn oligomers plus fibrils but not the oligomers by themselves under the 10-day dosing regimen. In contrast, using ELISA, high levels of serum autoantibodies to alpha-syn monomeric, oligomeric and fibrillar conformers as well as DA were observed in both treatment groups reflecting immune system activation and this substantiates previous clinical studies in Parkinson's disease patients. Thus, nasal administration of alpha-syn amyloidogenic species may be a potential experimental PD model which results not only in motor deficits but also incitement of humoral protection to mimic the disease. Such a paradigm may be exploitable in the quest for potential therapeutic strategies and further studies are warranted.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng
653 a alpha-Synuclein oligomers
653 a Fibrils
653 a Rigidity
653 a Locomotor activity
653 a Autoantibodies
653 a Dopamine
653 a Rodent
7001 a Davidova, Tatiana V.4 aut
7001 a Yanamandra, Kiranu Umeå universitet,Institutionen för medicinsk kemi och biofysik4 aut
7001 a Kucheryanu, Valery G.4 aut
7001 a Morozova-Roche, Ludmilla A.u Umeå universitet,Institutionen för medicinsk kemi och biofysik4 aut0 (Swepub:umu)lumo0001
7001 a Sherstnev, Vladimir V.4 aut
7001 a Sewell, Robert D. E.4 aut
7102 a Umeå universitetb Institutionen för medicinsk kemi och biofysik4 org
7730 t Behavioural Brain Researchd : Elsevier BVg 243, s. 205-212q 243<205-212x 0166-4328x 1872-7549
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-71313
8564 8u https://doi.org/10.1016/j.bbr.2013.01.011

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