Time course and magnitude of alpha-synuclein inclusion formation and nigrostriatal degeneration in the rat model of synucleinopathy triggered by intrastriatal α-synuclein preformed fibrils.
Neurobiol Dis
; 130: 104525, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31276792
ABSTRACT
Animal models that accurately recapitulate the accumulation of alpha-synuclein (α-syn) inclusions, progressive neurodegeneration of the nigrostriatal system and motor deficits can be useful tools for Parkinson's disease (PD) research. The preformed fibril (PFF) synucleinopathy model in rodents generally displays these PD-relevant features, however, the magnitude and predictability of these events is far from established. We therefore sought to optimize the magnitude of α-syn accumulation and nigrostriatal degeneration, and to understand the time course of both. Rats were injected unilaterally with different quantities of α-syn PFFs (8 or 16⯵g of total protein) into striatal sites selected to concentrate α-syn inclusion formation in the substantia nigra pars compacta (SNpc). Rats displayed an α-syn PFF quantity-dependent increase in the magnitude of ipsilateral SNpc inclusion formation at 2â¯months and bilateral loss of nigral dopamine neurons at 6â¯months. Unilateral 16⯵g PFF injection also resulted in modest sensorimotor deficits in forelimb adjusting steps associated with degeneration at 6â¯months. Bilateral injection of 16⯵g α-syn PFFs resulted in symmetric bilateral degeneration equivalent to the ipsilateral nigral degeneration observed following unilateral 16⯵g PFF injection (~50% loss). Bilateral PFF injections additionally resulted in alterations in several gait analysis parameters. These α-syn PFF parameters can be applied to generate a reproducible synucleinopathy model in rats with which to study pathogenic mechanisms and vet potential disease-modifying therapies.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Substância Negra
/
Corpo Estriado
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Alfa-Sinucleína
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Sinucleinopatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Ano de publicação:
2019
Tipo de documento:
Article