Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates

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Fältnamn	Indikatorer	Metadata
000		03867naa a2200409 4500
001		oai:DiVA.org:umu-88668
003		SwePub
008		140512s2014 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-886682 URI
024	7	a https://doi.org/10.1016/j.bbr.2014.01.0172 DOI
040		a (SwePub)umu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Gruden, Marina A4 aut
245	1 0	a Intranasal administration of alpha-synuclein aggregates :b a Parkinson's disease model with behavioral and neurochemical correlates
264	1	b Elsevier,c 2014
338		a print2 rdacarrier
520		a Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (alpha-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with alpha-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries. In vitro generated alpha-syn oligomers and fibrils were characterized using atomic force microscopy and the thioflavin T binding assay. These toxic oligomers or fibrils administered alone (0.48 mg/kg) or their 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behavior was tested on days 0, 15 and 28 of the protocol. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e., 14 days after treatment completion) induced rigidity, hypokinesia and immobility. This was accompanied by elevated nigral but not striatal DA, DOPAC and HVA concentrations in response to dual administration of alpha-syn oligomers plus fibrils but not the oligomers by themselves. alpha-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the substantia nigra. Only nigral DA turnover (DOPAC/DA but not HVA/DA ratio) was augmented in response to fibril treatment but there were no changes in the striatum. Compilation of these novel behavioral and neurochemical findings substantiate the validity of the alpha-syn nasal vector model for investigating parkinsonian-like symptoms.(C) 2014 Elsevier B.V. All rights reserved.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
653		a Rodent model; α-synuclein oligomers; Fibrils; Behavior; Dopamine neurochemistry
700	1	a Davydova, Tatiana V4 aut
700	1	a Narkevich, Victor B4 aut
700	1	a Fomina, Valentina G4 aut
700	1	a Wang, Chaou Umeå universitet,Institutionen för medicinsk kemi och biofysik4 aut0 (Swepub:umu)chwa0028
700	1	a Kudrin, Vladimir S4 aut
700	1	a Morozova-Roche, Ludmilla Au Umeå universitet,Institutionen för medicinsk kemi och biofysik4 aut0 (Swepub:umu)lumo0001
700	1	a Sewell, Robert DE4 aut
710	2	a Umeå universitetb Institutionen för medicinsk kemi och biofysik4 org
773	0	t Behavioural Brain Researchd : Elsevierg 263, s. 158-168q 263<158-168x 0166-4328x 1872-7549
856	4	u https://orca.cardiff.ac.uk/59157/1/0%20MS%20Gruden%20Final%20BBR%20MASTER%20ORCA.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88668
856	4 8	u https://doi.org/10.1016/j.bbr.2014.01.017

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Av författaren/redakt...: Gruden, Marina A; Davydova, Tatian ...; Narkevich, Victo ...; Fomina, Valentin ...; Wang, Chao; Kudrin, Vladimir ...; visa fler...; Morozova-Roche, ...; Sewell, Robert D ...; visa färre...

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