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A Combined α-Synuclein/Fibril (SynFib) Model of Parkinson-Like Synucleinopathy Targeting the Nigrostriatal Dopamine System

Björklund, Anders LU orcid ; Nilsson, Fredrik LU orcid ; Mattsson, Bengt LU ; Hoban, Deirdre B LU and Parmar, Malin LU orcid (2022) In Journal of Parkinson's Disease 12(8). p.2307-2320
Abstract

Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response... (More)

Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response induced by the PFF seeds in the presence of an elevated α-synuclein level. Injection of the AAV/PFF mixture into the substantia nigra makes it possible to target a larger proportion of the nigral dopamine neurons and obtain a level of dopamine cell loss (>60%) needed to induce significant impairments in drug-induced and spontaneous motor tests. The SynFib model shares attractive features of the standard 6-OHDA lesion model: a single unilateral stereotaxic intervention; pathology and cell loss developing over a short time span; and the possibility to monitor the degenerative changes using tests of motor behavior.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Parkinson's Disease
volume
12
issue
8
pages
14 pages
publisher
IOS Press
external identifiers
  • pmid:36189605
  • scopus:85144637844
ISSN
1877-718X
DOI
10.3233/JPD-223452
language
English
LU publication?
yes
id
dcdbb17d-8ec0-4501-9107-58734376e96e
date added to LUP
2022-10-14 10:46:02
date last changed
2024-06-29 00:05:41
@article{dcdbb17d-8ec0-4501-9107-58734376e96e,
  abstract     = {{<p>Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response induced by the PFF seeds in the presence of an elevated α-synuclein level. Injection of the AAV/PFF mixture into the substantia nigra makes it possible to target a larger proportion of the nigral dopamine neurons and obtain a level of dopamine cell loss (&gt;60%) needed to induce significant impairments in drug-induced and spontaneous motor tests. The SynFib model shares attractive features of the standard 6-OHDA lesion model: a single unilateral stereotaxic intervention; pathology and cell loss developing over a short time span; and the possibility to monitor the degenerative changes using tests of motor behavior.</p>}},
  author       = {{Björklund, Anders and Nilsson, Fredrik and Mattsson, Bengt and Hoban, Deirdre B and Parmar, Malin}},
  issn         = {{1877-718X}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{8}},
  pages        = {{2307--2320}},
  publisher    = {{IOS Press}},
  series       = {{Journal of Parkinson's Disease}},
  title        = {{A Combined α-Synuclein/Fibril (SynFib) Model of Parkinson-Like Synucleinopathy Targeting the Nigrostriatal Dopamine System}},
  url          = {{http://dx.doi.org/10.3233/JPD-223452}},
  doi          = {{10.3233/JPD-223452}},
  volume       = {{12}},
  year         = {{2022}},
}