Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

A. Slézia, P. Hegedüs, E. Rusina, K. Lengyel, N. Solari, A. Kaszas, D. Balázsfi, B. Botzanowski, E. Acerbo, F. Missey, A. Williamson, B. Hangya

. 2023 ; 13 (1) : 19478. [pub] 20231109

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc24000710

Studying animal models furthers our understanding of Parkinson'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's disease in mice.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24000710
003      
CZ-PrNML
005      
20240213093329.0
007      
ta
008      
240109s2023 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/s41598-023-46576-0 $2 doi
035    __
$a (PubMed)37945922
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Slézia, Andrea $u Institute of Experimental Medicine, Lendület Laboratory of Systems Neuroscience, Budapest, Hungary. andrea.slezia@gmail.com $u Institut de Neurosciences Des Systèmes, INSERM UMR S 1106, Aix-Marseille Université, Marseille, France. andrea.slezia@gmail.com $u Institute of Cognitive Neuroscience and Psychology, Eotvos Lorand Research Network, Budapest, Hungary. andrea.slezia@gmail.com $u Institut de Neurosciences de la Timone, CNRS UMR 7289, Aix-Marseille Université, Marseille, France. andrea.slezia@gmail.com
245    10
$a Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease / $c A. Slézia, P. Hegedüs, E. Rusina, K. Lengyel, N. Solari, A. Kaszas, D. Balázsfi, B. Botzanowski, E. Acerbo, F. Missey, A. Williamson, B. Hangya
520    9_
$a Studying animal models furthers our understanding of Parkinson'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's disease in mice.
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a myši $7 D051379
650    _2
$a zvířata $7 D000818
650    12
$a Parkinsonova nemoc $x etiologie $x patologie $7 D010300
650    _2
$a oxidopamin $x farmakologie $7 D016627
650    _2
$a pars compacta $x metabolismus $7 D065842
650    _2
$a dopamin $x metabolismus $7 D004298
650    _2
$a dopaminergní neurony $x metabolismus $7 D059290
650    _2
$a modely nemocí na zvířatech $7 D004195
650    _2
$a substantia nigra $x metabolismus $7 D013378
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Hegedüs, Panna $u Institute of Experimental Medicine, Lendület Laboratory of Systems Neuroscience, Budapest, Hungary $u János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary
700    1_
$a Rusina, Evgeniia $u Institut de Neurosciences Des Systèmes, INSERM UMR S 1106, Aix-Marseille Université, Marseille, France
700    1_
$a Lengyel, Katalin $u Institute of Experimental Medicine, Lendület Laboratory of Systems Neuroscience, Budapest, Hungary
700    1_
$a Solari, Nicola $u Institute of Experimental Medicine, Lendület Laboratory of Systems Neuroscience, Budapest, Hungary
700    1_
$a Kaszas, Attila $u Institut de Neurosciences de la Timone, CNRS UMR 7289, Aix-Marseille Université, Marseille, France
700    1_
$a Balázsfi, Diána $u Institute of Experimental Medicine, Lendület Laboratory of Systems Neuroscience, Budapest, Hungary
700    1_
$a Botzanowski, Boris $u Institut de Neurosciences Des Systèmes, INSERM UMR S 1106, Aix-Marseille Université, Marseille, France
700    1_
$a Acerbo, Emma $u Institut de Neurosciences Des Systèmes, INSERM UMR S 1106, Aix-Marseille Université, Marseille, France
700    1_
$a Missey, Florian $u Institut de Neurosciences Des Systèmes, INSERM UMR S 1106, Aix-Marseille Université, Marseille, France
700    1_
$a Williamson, Adam $u Institut de Neurosciences Des Systèmes, INSERM UMR S 1106, Aix-Marseille Université, Marseille, France. adam.williamson@fnusa.cz $u International Clinical Research Center (ICRC), St. Anne's University Hospital, Brno, Czech Republic. adam.williamson@fnusa.cz
700    1_
$a Hangya, Balázs $u Institute of Experimental Medicine, Lendület Laboratory of Systems Neuroscience, Budapest, Hungary. hangya.balazs@koki.hu
773    0_
$w MED00182195 $t Scientific reports $x 2045-2322 $g Roč. 13, č. 1 (2023), s. 19478
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37945922 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240109 $b ABA008
991    __
$a 20240213093326 $b ABA008
999    __
$a ok $b bmc $g 2049375 $s 1210404
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 13 $c 1 $d 19478 $e 20231109 $i 2045-2322 $m Scientific reports $n Sci Rep $x MED00182195
LZP    __
$a Pubmed-20240109

Find record

Citation metrics

Archiving options