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

Title

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

Creator

Patterson Joseph R; Duffy Megan F; Kemp Christopher J; Howe Jacob W; Collier Timothy J; Stoll Anna C; Miller Kathryn M; Patel Pooja; Levine Nathan; Moore Darren J; Luk Kelvin C; Fleming Sheila M; Kanaan Nicholas M; Paumier Katrina L; El-Agnaf Omar M A; Sortwell Caryl E

Publisher

Neurobiology of Disease

Date

2019
2019-10

Description

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 μg 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 2 months and bilateral loss of nigral dopamine neurons at 6 months. Unilateral 16 μg PFF injection also resulted in modest sensorimotor deficits in forelimb adjusting steps associated with degeneration at 6 months. Bilateral injection of 16 μg α-syn PFFs resulted in symmetric bilateral degeneration equivalent to the ipsilateral nigral degeneration observed following unilateral 16 μg 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.

Subject

Alpha-Synuclein; PARKINSON'S disease; Preformed fibrils; Synucleinopathy

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

104525-104525

Volume

130

Citation

Patterson Joseph R; Duffy Megan F; Kemp Christopher J; Howe Jacob W; Collier Timothy J; Stoll Anna C; Miller Kathryn M; Patel Pooja; Levine Nathan; Moore Darren J; Luk Kelvin C; Fleming Sheila M; Kanaan Nicholas M; Paumier Katrina L; El-Agnaf Omar M A; Sortwell Caryl E, “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,” NEOMED Bibliography Database, accessed June 21, 2021, https://neomed.omeka.net/items/show/6505.

Social Bookmarking