Brain-specific NRSF deficiency aggravates dopaminergic neurodegeneration and impairs neurogenesis in the MPTP mouse model of Parkinson's disease.
Aging (Albany NY)
; 11(10): 3280-3297, 2019 05 30.
Article
en En
| MEDLINE
| ID: mdl-31147527
Degeneration of the dopaminergic neurons in the substantia nigra and the resultant dopamine depletion from the striatum are the hallmarks of Parkinson's disease (PD) and are responsible for the disease's cardinal motor symptoms. The transcriptional repressor Neuron-Restrictive Silencer Factor (NRSF), also known as RE1-Silencing Transcription Factor (REST), was originally identified as a negative regulator of neuron-specific genes in non-neuronal cells. Our previous study showed that mice deficient in neuronal NRSF/REST expression were more vulnerable to the noxious effects of the dopaminergic neurotoxin MPTP. Here, we found that brain-specific deletion of NRSF/REST led to more severe damages to the nigrostriatal pathway and long-lasting behavioral impairments in mice challenged with MPTP. Moreover, compared to wild-type controls, these mice showed increased neurogenesis shortly after MPTP exposure, but reduced neurogenesis later on. These results suggest that NRSF/REST acts as a negative modulator of neurogenesis and a pro-survival factor of neural stem cells under both normal conditions and during the course of PD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Encéfalo
/
Intoxicación por MPTP
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Neurogénesis
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Neuronas Dopaminérgicas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos