Neurovascular and immune factors of vulnerability of substantia nigra dopaminergic neurons in non-human primates.
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:
17 Jun 2024
17 Jun 2024
Historique:
received:
20
11
2023
accepted:
30
05
2024
medline:
18
6
2024
pubmed:
18
6
2024
entrez:
17
6
2024
Statut:
epublish
Résumé
Dopaminergic neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease (PD), while those in the dorsal tier and ventral tegmental area are relatively spared. The factors determining why these neurons are more vulnerable than others are still unrevealed. Neuroinflammation and immune cell infiltration have been demonstrated to be a key feature of neurodegeneration in PD. However, the link between selective dopaminergic neuron vulnerability, glial and immune cell response, and vascularization and their interactions has not been deciphered. We aimed to investigate the contribution of glial cell activation and immune cell infiltration in the selective vulnerability of ventral dopaminergic neurons within the midbrain in a non-human primate model of PD. Structural characteristics of the vasculature within specific regions of the midbrain were also evaluated. Parkinsonian monkeys exhibited significant microglial and astroglial activation in the whole midbrain, but no major sub-regional differences were observed. Remarkably, the ventral substantia nigra was found to be typically more vascularized compared to other regions. This feature might play some role in making this region more susceptible to immune cell infiltration under pathological conditions, as greater infiltration of both T- and B- lymphocytes was observed in parkinsonian monkeys. Higher vascular density within the ventral region of the SNc may be a relevant factor for differential vulnerability of dopaminergic neurons in the midbrain. The increased infiltration of T- and B- cells in this region, alongside other molecules or toxins, may also contribute to the susceptibility of dopaminergic neurons in PD.
Identifiants
pubmed: 38886348
doi: 10.1038/s41531-024-00735-w
pii: 10.1038/s41531-024-00735-w
doi:
Types de publication
Journal Article
Langues
eng
Pagination
118Subventions
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CP19/00200
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PI20/00496
Organisme : Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid)
ID : PID2019-111045RB-100
Organisme : Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid)
ID : S2017/BMD-3700
Informations de copyright
© 2024. The Author(s).
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