NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

• Published in: Biochemical and biophysical research communications Vol. 411; no. 4; pp. 667 - 672
• Main Authors: Li, Mei, Zhang, Dong-Qing, Wang, Xiang-Zhen, Xu, Tie-Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.08.2011
• Subjects: 60 APPLIED LIFE SCIENCES; AMP; Animals; CALCIUM; Calcium-Calmodulin-Dependent Protein Kinase Type 4 - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 4 - metabolism; CALMODULIN; CaMKIV; CELL PROLIFERATION; Cells, Cultured; CREB; Cyclic AMP Response Element-Binding Protein - metabolism; Hippocampus - cytology; Neural Stem Cells - metabolism; Neural Stem Cells - physiology; Neural stem/progenitor cells; NR2B; PHOSPHATES; PHOSPHORYLATION; POLYMERASE CHAIN REACTION; Proliferation; Rats; Rats, Sprague-Dawley; RECEPTORS; Receptors, N-Methyl-D-Aspartate - metabolism; RNA; TRANSCRIPTION; PBS; CaMKIV; TBST; NSPCs; siRNA; Proliferation; NR2B; CREB; ANOVA; RT-PCR; NMDA; CCK-8; NMDAR; LSD; Neural stem/progenitor cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.06.170

► The NR2B component of the NMDARs is important for the NSPC proliferation. ► pCaMKIV and pCREB exist in NSPCs. ► The CaMKIV/CREB pathway mediates NSPC proliferation. Accumulating evidence indicates the involvement of N-methyl-d-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.