AMPK Plays a Dual Role in Regulation of CREB/BDNF Pathway in Mouse Primary Hippocampal Cells

作者：Huang, Weidong^*; Cao, Jie; Liu, Xiaobin; Meng, Facai; Li, Min; Chen, Bo; Zhang, Jie

来源：Journal of Molecular Neuroscience, 2015, 56(4): 782-788.

DOI：10.1007/s12031-015-0500-2

• Hippocampal neurons
• AMPK
• CREB
• SIRT1/miR-134
• Dual role

The hippocampus is vulnerable to damage under conditions of ischemia and hypoxia, causing multiple mental illnesses. cAMP response element-binding protein (CREB) plays a pivotal role in preventing the apoptosis of neurons and many other cells. Here, we found that AMP-activated protein kinase (AMPK) and CREB are oppositely regulated in mouse primary hippocampal neurons impaired by hypoxia-hypoglycemia. AMPK overexpression reduced the CREB level by upregulating SIRT1 and was negatively posttranscriptionally regulated by miR-134, suggesting a negative regulatory role of AMPK in the expression of CREB. Interestingly, the downstream genes of CREB, brain-derived neurotrophic factor (BDNF), and Bcl-2 remained unchanged when CREB was downregulated by AMPK expression. In addition, in AMPK(-/-)primary hippocampal neurons, comparisons between the effect of upregulation and silencing of miR-134 on the expression of CREB, BDNF, and Bcl-2 were made. The results reveal that AMPK is crucial for the activation of CREB via phosphorylation. Therefore, AMPK plays a dual role in the regulation of CREB in mouse primary hippocampal cells: a negative effect on total CREB expression by elevating SIRT1/miR-134 and a positive effect on activity via phosphorylation.

• 出版日期2015-8
• 单位陕西省人民医院