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Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
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Gruden, Marina A (författare)
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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, Chao (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Kudrin, Vladimir S (författare)
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- Morozova-Roche, Ludmilla A (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Sewell, Robert D E (författare)
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(creator_code:org_t)
- Elsevier BV, 2015
- Engelska.
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 279, s. 191-201
- Relaterad länk:
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https://orca.cardiff...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Nyckelord
- Rodent model
- alpha-synuclein oligomers & fibrils
- Behavior
- Noradrenaline
- 5-HT
- Metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)