Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
2014 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 279, 191-201 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 279, 191-201 p.
Other Basic Medicine
IdentifiersURN: urn:nbn:se:umu:diva-97014DOI: 10.1016/j.bbr.2014.11.001ISI: 000348255200024PubMedID: 25446742OAI: oai:DiVA.org:umu-97014DiVA: diva2:769696