Send to

Choose Destination
Aging (Albany NY). 2019 May 30;11(10):3280-3297. doi: 10.18632/aging.101979.

Brain-specific NRSF deficiency aggravates dopaminergic neurodegeneration and impairs neurogenesis in the MPTP mouse model of Parkinson's disease.

Author information

Department of Translational Neuroscience, Jing' an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
School of Life Science and Technology, Tongji University, Shanghai 200092, China.
Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, Inc., Shanghai 201203, China.
Contributed equally


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.


NRSF/REST; Parkinson’s disease; astrocyte activation; neurodegeneration; neuroinflammation

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center