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Updated: May 2, 2026
Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
MAF1 loss protects against ischemic cerebral injury by attenuating NLRP3-mediated pyroptosis
Xue Gao1, Hanzhi Wang1, Lingting Jin1
1Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Background:
Acute ischemic stroke (AIS) is the second leading cause of death worldwide and is associated with high rates of disability and mortality. Emerging evidence indicates that the transcriptional regulator MAF1 may play an important role in neurological diseases by modulating the NLRP3 signaling pathway. Previous studies suggest the transcriptional regulator MAF1 may play an important role in neurological diseases through regulating NLRP3 pathway. However, its role in ischemic cerebral injury remains unclear. This study aims to reveal the key role and mechanisms of MAF1 in AIS.
Methods:
Using transient middle cerebral artery occlusion (tMCAO) model, the sensorimotor function of mice after modeling was evaluated by behavioral methods and changes of MAF1 expression were investigated by Polymerase Chain Reaction (PCR), Western blot and Immunofluorescence (IF) staining. The oxygen glucose deprivation/reperfusion (OGD/R) model was used as cell model for in vitro verification. Stereotactic injection of AAV-hsyn-shMAF1 was used to assess the effect of MAF1 knockdown on the improvement of neurological function and infarct volume in stroke mice. RNA sequencing was performed to identify differentially expressed genes between OGD/R-Lenti-shMAF1 and OGD/R-Lenti-SCR groups. Western blot analysis was further applied to examine molecular alterations in the downstream NLRP3 pathway.
Results:
Expression of the transcription factor MAF1 was upregulated in AIS and conditional Conditional knockdown of MAF1 in the tMCAO mouse model alleviated neurological deficits and reduced infarct volume. RNA sequencing revealed altered expression of NLRP3-related pyroptosis proteins and pathways following MAF1 knockdown in OGD/R-treated primary neurons. Downregulation of MAF1 led to expression changes of NLRP3 inflammasome/pyroptosis pathways in both tMCAO mouse and OGD/R cell models.
Conclusions:
MAF1 expression was significantly increased in animal and cellular models of AIS. Knockdown of MAF1 improved neurological function after AIS and the protective effect is related to the regulation of the NLRP3 inflammasome/pyroptosis pathway. These findings elucidated a critical role and mechanistic insight for MAF1 in AIS pathogenesis, highlighting its potential as a therapeutic target for ischemic stroke treatment.
