Aldehyde dehydrogenase 1-positive nigrostriatal dopaminergic fibers exhibit distinct projection pattern and dopamine release dynamics at mouse dorsal striatum.
Sci Rep
; 7(1): 5283, 2017 07 13.
Article
em En
| MEDLINE
| ID: mdl-28706191
ABSTRACT
Aldehyde dehydrogenase 1 (ALDH1A1)-positive dopaminergic (DA) neurons at the ventral substantia nigra pars compacta (SNpc) preferentially degenerate in Parkinson's disease (PD). Their projection pattern and dopamine release properties, however, remains uncharacterized. Here we show that ALDH1A1-positive axons project predominantly to the rostral two-thirds of dorsal striatum. A portion of these axons converge on a small fraction of striosome compartments restricted to the dorsolateral striatum (DLS), where less dopamine release was measured compared to the adjacent matrix enriched with the ALDH1A1-negative axons. Genetic ablation of Aldh1a1 substantially increases the dopamine release in striosomes, but not in matrix. Additionally, the presence of PD-related human α-synuclein A53T mutant or dopamine transporter (DAT) blockers also differentially affects the dopamine output in striosomes and matrix. Together, these results demonstrate distinct dopamine release characteristics of ALDH1A1-positive DA fibers, supporting a regional specific function of ALDH1A1 in regulating dopamine availability/release in striatum.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Dopamina
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Proteínas de Homeodomínio
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Corpo Estriado
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Aldeído Desidrogenase
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Alfa-Sinucleína
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Neurônios Dopaminérgicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos