Characterisation of functional deficits induced by AAV overexpression of alpha-synuclein in rats.
AAV
Alpha-synuclein
Choice reaction time
Parkinson's disease
Visuo-spatial neglect
Journal
Current research in neurobiology
ISSN: 2665-945X
Titre abrégé: Curr Res Neurobiol
Pays: Netherlands
ID NLM: 101778135
Informations de publication
Date de publication:
2023
2023
Historique:
received:
11
09
2022
revised:
22
11
2022
accepted:
01
12
2022
entrez:
12
1
2023
pubmed:
13
1
2023
medline:
13
1
2023
Statut:
epublish
Résumé
In the last decades different preclinical animal models of Parkinson's disease (PD) have been generated, aiming to mimic the progressive neuronal loss of midbrain dopaminergic (DA) cells as well as motor and non-motor impairment. Among all the available models, AAV-based models of human alpha-synuclein (h-aSYN) overexpression are promising tools for investigation of disease progression and therapeutic interventions. The goal with this work was to characterise the impairment in motor and non-motor domains following nigrostriatal overexpression of h-aSYN and correlate the behavioural deficits with histological assessment of associated pathology. Intranigral injection of an AAV9 expressing h-aSYN was compared with untreated animals, 6-OHDA and AAV9 expressing either no transgene or GFP. The animals were assessed on a series of simple and complex behavioural tasks probing motor and non-motor domains. Post-mortem neuropathology was analysed using immunohistochemical methods. Overexpression of h-aSYN led to progressive degeneration of DA neurons of the SN and axonal terminals in the striatum (STR). We observed extensive nigral and striatal pathology, resembling that of human PD brain, as well as the development of stable progressive deficit in simple motor tasks and in non-motor domains such as deficits in motivation and lateralised neglect. In the present work we characterized a rat model of PD that closely resembles human PD pathology at the histological and behavioural level. The correlation of cell loss with behavioural performance enables the selection of rats which can be used in neuroprotective or neurorestorative therapies.
Sections du résumé
Background
UNASSIGNED
In the last decades different preclinical animal models of Parkinson's disease (PD) have been generated, aiming to mimic the progressive neuronal loss of midbrain dopaminergic (DA) cells as well as motor and non-motor impairment. Among all the available models, AAV-based models of human alpha-synuclein (h-aSYN) overexpression are promising tools for investigation of disease progression and therapeutic interventions.
Objectives
UNASSIGNED
The goal with this work was to characterise the impairment in motor and non-motor domains following nigrostriatal overexpression of h-aSYN and correlate the behavioural deficits with histological assessment of associated pathology.
Methods
UNASSIGNED
Intranigral injection of an AAV9 expressing h-aSYN was compared with untreated animals, 6-OHDA and AAV9 expressing either no transgene or GFP. The animals were assessed on a series of simple and complex behavioural tasks probing motor and non-motor domains. Post-mortem neuropathology was analysed using immunohistochemical methods.
Results
UNASSIGNED
Overexpression of h-aSYN led to progressive degeneration of DA neurons of the SN and axonal terminals in the striatum (STR). We observed extensive nigral and striatal pathology, resembling that of human PD brain, as well as the development of stable progressive deficit in simple motor tasks and in non-motor domains such as deficits in motivation and lateralised neglect.
Conclusions
UNASSIGNED
In the present work we characterized a rat model of PD that closely resembles human PD pathology at the histological and behavioural level. The correlation of cell loss with behavioural performance enables the selection of rats which can be used in neuroprotective or neurorestorative therapies.
Identifiants
pubmed: 36632447
doi: 10.1016/j.crneur.2022.100065
pii: S2665-945X(22)00038-9
pmc: PMC9827042
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100065Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK108798
Pays : United States
Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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