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RESEARCH PRODUCT

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

subject

description

Synaptic protein -synuclein (-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinsons disease. Here, we report that -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. We also showthat premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking-SYN resemblesthe 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 -SYN. Interestingly, NSC loss in -SYN-deficient mice can be prevented by viral delivery of human -SYN into their sustantia nigra or by treatment with L-DOPA, suggesting that -SYN regulates dopamine availability to NSCs. Our data indicatethat-SYN, presentin dopaminergic nerveterminals supplyingthe subependymal zone, acts as a niche componentto sustainthe neurogenic potential of adult NSCs and identify -SYN and DA as potential targets to ameliorate neurogenic defects in the aging and diseased brain.