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Review
. 2022 Jul;12(7):e2628.
doi: 10.1002/brb3.2628. Epub 2022 Jun 1.

Modeling Parkinson's disease-related symptoms in alpha-synuclein overexpressing mice

Agata Aniszewska  1 , Joakim Bergström  1 , Martin Ingelsson  1   2   3 , Sara Ekmark-Lewén  1
Affiliations
Review

Modeling Parkinson's disease-related symptoms in alpha-synuclein overexpressing mice

Agata Aniszewska et al. Brain Behav. 2022 Jul.

Abstract

Background: Intracellular deposition of alpha-synuclein (α-syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α-synucleinopathies. Transgenic mouse models overexpressing human α-syn, are useful research tools in preclinical studies of pathogenetic mechanisms. Such mice develop α-syn inclusions as well as neurodegeneration with a topographical distribution that varies depending on the choice of promoter and which form of α-syn that is overexpressed. Moreover, they display motor symptoms and cognitive disturbances that to some extent resemble the human conditions.

Purpose: One of the main motives for assessing behavior in these mouse models is to evaluate the potential of new treatment strategies, including their impact on motor and cognitive symptoms. However, due to a high within-group variability with respect to such features, the behavioral studies need to be applied with caution. In this review, we discuss how to make appropriate choices in the experimental design and which tests that are most suitable for the evaluation of PD-related symptoms in such studies.

Methods: We have evaluated published results on two selected transgenic mouse models overexpressing wild type (L61) and mutated (A30P) α-syn in the context of their validity and utility for different types of behavioral studies.

Conclusions: By applying appropriate behavioral tests, α-syn transgenic mouse models provide an appropriate experimental platform for studies of symptoms related to PD and other α-synucleinopathies.

Keywords: Parkinson´s disease; alpha-synuclein; behavioral test; ethology; transgenic mouse models; translational research.

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Conflict of interest statement

Martin Ingelsson is a paid consultant to BioArctic AB. The other authors do not have any conflict of interest.

Figures

FIGURE 1
FIGURE 1
Aggregation pathway, toxicity (a) and propagation (b) of α‐synuclein in the PD brain. Created with BioRender
FIGURE 2
FIGURE 2
Brief characterization of selected SNCA transgenic mouse models of PD, including the pattern of α‐synuclein pathology, motor symptoms, and age of symptom onset. Created with BioRender
FIGURE 3
FIGURE 3
Summary of behavioral tests and procedures used to assess the most common motor and nonmotor symptoms observed in mouse models of PD. Created with BioRender
FIGURE 4
FIGURE 4
The multivariate concentric square field (MCSF) test is used to assess ethologically relevant behaviors in an environment that recapitulates features observed in the natural habitats of rodents. The arena includes central areas suitable for measurements of basic locomotor activity and exploration, as well as side areas designed to assess specific behavioral features, e.g. anxiety‐like behaviors or risk taking. Created with BioRender
See this image and copyright information in PMC

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