Cortical Lewy body injections induce long-distance pathogenic alterations in the non-human primate brain.
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
19 Sep 2023
19 Sep 2023
Historique:
received:
05
05
2023
accepted:
08
09
2023
medline:
20
9
2023
pubmed:
20
9
2023
entrez:
19
9
2023
Statut:
epublish
Résumé
Aggregation of α-synuclein (α-syn) is the cornerstone of neurodegenerative diseases termed synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). These synucleinopathies are characterized by the deposit of aggregated α-syn in intracellular inclusions observable in neurons and glial cells. In PD and DLB, these aggregates, predominantly located in neurons, are called Lewy Bodies (LBs). These LBs are one of the pathological hallmarks of PD and DLB, alongside dopaminergic neuron loss in the substantia nigra. Previous studies have demonstrated the ability of PD patient-derived LB fractions to induce nigrostriatal neurodegeneration and α-syn pathology when injected into the striatum or the enteric nervous system of non-human primates. Here, we report the pathological consequences of injecting these LB fractions into the cortex of non-human primates. To this end, we inoculated mesencephalic PD patient-derived LB fractions into the prefrontal cortex of baboon monkeys terminated one year later. Extensive analyses were performed to evaluate pathological markers known to be affected in LB pathologies. We first assessed the hypothesized presence of phosphorylated α-syn at S129 (pSyn) in the prefrontal cortices. Second, we quantified the neuronal, microglial, and astrocytic cell survival in the same cortices. Third, we characterized these cortical LB injections' putative impact on the integrity of the nigrostriatal system. Overall, we observed pSyn accumulation around the injection site in the dorsal prefrontal cortex, in connected cortical regions, and further towards the striatum, suggesting α-syn pathological propagation. The pathology was also accompanied by neuronal loss in these prefrontal cortical regions and the caudate nucleus, without, however, loss of nigral dopamine neurons. In conclusion, this pilot study provides novel data demonstrating the toxicity of patient-derived extracts, their potential to propagate from the cortex to the striatum in non-human primates, and a possible primate model of DLB.
Identifiants
pubmed: 37726343
doi: 10.1038/s41531-023-00579-w
pii: 10.1038/s41531-023-00579-w
pmc: PMC10509171
doi:
Types de publication
Journal Article
Langues
eng
Pagination
135Subventions
Organisme : Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)
ID : 2013-8499
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : 12-BSV4-0001-01
Informations de copyright
© 2023. Springer Nature Limited.
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