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

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Gruden, Marina A (author)

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

Article/chapterEnglish2014

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Elsevier,2014
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LIBRIS-ID:oai:DiVA.org:umu-88668
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88668URI
https://doi.org/10.1016/j.bbr.2014.01.017DOI

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Language:English
Summary in:English

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
Rodent model; α-synuclein oligomers; Fibrils; Behavior; Dopamine neurochemistry

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Davydova, Tatiana V (author)
Narkevich, Victor B (author)
Fomina, Valentina G (author)
Wang, ChaoUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)chwa0028 (author)
Kudrin, Vladimir S (author)
Morozova-Roche, Ludmilla AUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)lumo0001 (author)
Sewell, Robert DE (author)
Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

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In:Behavioural Brain Research: Elsevier263, s. 158-1680166-43281872-7549

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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