Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells

Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and...

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Detalles Bibliográficos
Autores: Pérez Villalba, Ana, Sirerol‑Piquer, María Salomé, Belenguer, Germán, Soriano‑Cantón, Raúl, Muñoz-Manchado, Ana Belén, Villadiego, Javier, Alarcón-Arís, Diana, Soria, Federico N., Dehay, Benjamin, Bezard, Erwan, Vila, Miquel, Bortolozzi, Analía, Toledo-Aral, Juan José, Pérez-Sánchez, Francisco, Fariñas, Isabel
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Católica de Valencia San Vicente Mártir
Repositorio:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglés
OAI Identifier:oai:riucv.ucv.es:20.500.12466/5675
Acceso en línea:http://hdl.handle.net/20.500.12466/5675
Access Level:acceso abierto
Palabra clave:Adult neurogenesis
Niche biology
Parkinsonism
Snca knock-out
Stemness
2490 Neurociencias
Descripción
Sumario:Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice.Wealso show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic α-SYN. Interestingly, NSC loss in α-SYN-deficient mice can be prevented by viral delivery of human α-SYN into their sustantia nigra or by treatment with L-DOPA, suggesting that α-SYN regulates dopamine availability to NSCs. Our data indicate that α-SYN, present in dopaminergic nerve terminals supplying the subependymal zone, acts as a niche component to sustain the neurogenic potential of adult NSCs and identify α-SYN and DA as potential targets to ameliorate neurogenic defects in the aging and diseased brain.

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