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Noradrenergic and s...
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Gruden, Marina A
(författare)
Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
- Artikel/kapitelEngelska2015
Förlag, utgivningsår, omfång ...
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Elsevier BV,2015
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-97014
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-97014URI
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https://doi.org/10.1016/j.bbr.2014.11.001DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay. Levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected using HPLC with electrochemical detection in the substantia nigra (SN) and striatum. The oligomers or fibrils administered alone or in a 50:50 combination (total dose of 0.48mg/kg) were given intranasally for 14 days and "open-field" behaviour was tested on days 0, 15 and 28 of the protocol, at which time brain structures were sampled. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e. 14 days after treatment completion) induced hypokinesia and immobility whilst the aggregate combination additionally produced rigidity. The α-Syn oligomer/fibril mixture also instigated PD-like motor symptoms which correlated heterochronically with elevated NA levels in the striatum but then later in the SN while intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations throughout the protocol. In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Neurodegenerative and/or actions on neurotransmitter transporters (such as NET, SERT and VMAT2) are discussed as being implicated in these α-syn amyloid induced neurochemical and motoric disturbances.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Davydova, Tatiana V
(författare)
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Narkevich, Victor B
(författare)
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Fomina, Valentina G
(författare)
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Wang, ChaoUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)chwa0028
(författare)
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Kudrin, Vladimir S
(författare)
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Morozova-Roche, Ludmilla AUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)lumo0001
(författare)
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Sewell, Robert D E
(författare)
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Umeå universitetInstitutionen för medicinsk kemi och biofysik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Behavioural Brain Research: Elsevier BV279, s. 191-2010166-43281872-7549
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