Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079711" target="_blank" >RIV/00159816:_____/23:00079711 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-023-46576-0" target="_blank" >https://www.nature.com/articles/s41598-023-46576-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-023-46576-0" target="_blank" >10.1038/s41598-023-46576-0</a>

Result language

angličtina

Original language name

Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease

Original language description

Studying animal models furthers our understanding of Parkinson&apos;s disease ( PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early onset, dose-dependent impairments of overall locomotion without substantial deterioration of motor coordination. In accordance, histological evaluation demonstrated a partial, dose-dependent loss of dopaminergic neurons of substantia nigra pars compacta (SNc). Furthermore, electron microscopic analysis revealed degenerative ultrastructural changes in SNc dopaminergic neurons. Our results show that mild ultrastructural and cellular degradation of dopaminergic neurons of the SNc can lead to certain motor deficits shortly after unilateral striatal lesions, suggesting that a unilateral dose-dependent intrastriatal 6-OHDA lesion protocol can serve as a successful model of the early stages of Parkinson&apos;s disease in mice.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

19478

UT code for WoS article

001106459000069

EID of the result in the Scopus database

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