کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6257348 1612953 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research reportNoradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Research reportNoradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
چکیده انگلیسی


- α-Synuclein fibrils and/or oligomers were given intranasally for 14 days in mice.
- Combined oligomers + fibrils caused rigidity and locomotor impairment.
- α-Syn mixture motor symptoms coincided with elevated striatal then later nigral NA.
- Fibrils augmented nigral 5-HT and 5-HIAA but an oligomer 5-HT effect was delayed.
- Neurodegenerative, vesicular and monoamine transporter mechanisms are discussed.

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 0.48 mg/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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 279, 15 February 2015, Pages 191-201
نویسندگان
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