Norepinephrine Induces BDNF and Activates CREB and Discriminates among Protein Kinase C Isoforms in Cultured Embryonic Hippocampal Neurons

作     者：Michael Chen Amelia Russo-Neustadt 

作者机构：Department of Biological Sciences California State University Los Angeles CA USA 

出 版 物：《Neuroscience & Medicine》 (神经系统科学与医药（英文）)

年 卷 期：2017年第8卷第4期

页      面：53-67页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：BDNF CREB PKD PKC Hippocampus 

摘      要：Medications acting as mood stabilizers work by enhancing and maintaining the concentration of circulating synaptic neurotransmitters, which then activate a plethora of various intracellular signal transduction and second messenger cascades. Previously, we showed that two of these cascades, the PI-3K and MAPK pathways, are activated by cross-talk with the protein kinase A cAMP cascade and by brain-derived neurotrophic factor (BDNF), an immediate-early gene whose expression is the result of phosphorylation of the transcription factor, cAMP response element binding protein (CREB). In the current study, we extend these findings to include the protein kinase C (PKC) pathway. Western blotting studies show that application of norepinephrine to cultured hippocampal neurons leads to increased expression of BDNF, phosphorylation of CREB, activation of growth-associated protein-43 (GAP-43) and activation of PKCμ and PKCt538. Because GAP-43 is a putative substrate for PKC, the results of this study lend further support of a G-protein coupled receptor cross-talking to an entirely distinct intracellular pathway that is known to be involved in neuritogenesis.