Effects of decreased dopamine transporter levels on nigrostriatal neurons and paraquat/maneb toxicity in mice.
Neurobiol Aging
; 51: 54-66, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-28038352
ABSTRACT
How genetic variations in the dopamine transporter (DAT) combined with exposure to environmental toxins modulate the risk of Parkinson's disease remains unclear. Using unbiased stereology in DAT knock-down mice (DAT-KD) and wild-type (WT) littermates, we found that decreased DAT caused a loss of tyrosine hydroxylase-positive (dopaminergic) neurons in subregions of the substantia nigra pars compacta at 3-4 days, 5 weeks, and 18 months of age. Both genotypes lost dopaminergic neurons with age and remaining neurons at 11 months were resilient to paraquat/maneb. In 5-week-old mice, the toxins decreased substantia nigra pars compacta dopaminergic neurons in both genotypes but less in DAT-KD. Regional analysis revealed striking differences in the subsets of neurons affected by low DAT, paraquat/maneb, and aging. In particular, we show that a potentially protective effect of low DAT against toxin exposure is not sufficient to reduce death of all nigrostriatal dopaminergic neurons. Thus, different regional vulnerability of nigrostriatal dopaminergic neurons may contribute to an increased risk of developing Parkinson's disease when multiple factors are combined.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraquat
/
Enfermedad de Parkinson
/
Variación Genética
/
Envejecimiento
/
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática
/
Neuronas Dopaminérgicas
/
Porción Compacta de la Sustancia Negra
/
Maneb
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Año:
2017
Tipo del documento:
Article