| Autor: |
Duperrier S; Institut des Sciences Cognitives Marc Jeannerod (ISCMJ), Unité Mixte de Recherche 5229 du Centre National de la Recherche Scientifique (CNRS), 69675 Bron, France.; UFR Biosciences, Université Claude Bernard, Lyon 1, 69100 Villeurbanne, France., Bortolozzi A; Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.; Biomedical Research Networking Center for Mental Health (CIBERSAM), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain., Sgambato V; Institut des Sciences Cognitives Marc Jeannerod (ISCMJ), Unité Mixte de Recherche 5229 du Centre National de la Recherche Scientifique (CNRS), 69675 Bron, France.; UFR Biosciences, Université Claude Bernard, Lyon 1, 69100 Villeurbanne, France. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2022 Aug 02; Vol. 23 (15). Date of Electronic Publication: 2022 Aug 02. |
| DOI: |
10.3390/ijms23158586 |
| Abstrakt: |
Parkinson's disease (PD) is characterized by cell loss in the substantia nigra and the presence of alpha-synuclein (α-syn)-containing neuronal Lewy bodies. While α-syn has received major interest in the pathogenesis of PD, the function of beta- and gamma-synucleins (β-syn and γ-syn, respectively) is not really known. Yet, these proteins are members of the same family and also concentrated in neuronal terminals. The current preclinical study investigated the expression levels of α-, β-, and γ-synucleins in brainstem regions involved in PD physiopathology. We analyzed synuclein expression in the substantia nigra, raphe nuclei, pedunculopontine nucleus, and locus coeruleus from control and parkinsonian (by MPTP) macaques. MPTP-intoxicated monkeys developed a more or less severe parkinsonian score and were sacrificed after a variable post-MPTP period ranging from 1 to 20 months. The expression of the three synucleins was increased in the substantia nigra after MPTP, and this increase correlates positively, although not very strongly, with cell loss and motor score and not with the time elapsed after intoxication. In the dorsal raphe nucleus, the expression of the three synucleins was also increased, but only α- and γ-Syn are linked to the motor score and associated cell loss. Finally, although no change in synuclein expression was demonstrated in the locus coeruleus after MPTP, we found increased expression levels of γ-Syn, which are only correlated with cell loss in the pedunculopontine nucleus. Altogether, our data suggest that these proteins may play a key role in brainstem regions and mesencephalic tegmentum. Given the involvement of these brain regions in non-motor symptoms of PD, these data also strengthen the relevance of the MPTP macaque model of PD, which exhibits pathological changes beyond nigral DA cell loss and α-synucleinopathy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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