TITLE:
Norepinephrine Induces BDNF and Activates CREB and Discriminates among Protein Kinase C Isoforms in Cultured Embryonic Hippocampal Neurons
AUTHORS:
Michael Chen, Amelia Russo-Neustadt
KEYWORDS:
BDNF, CREB, PKD, PKC, Hippocampus
JOURNAL NAME:
Neuroscience and Medicine,
Vol.8 No.4,
December
4,
2017
ABSTRACT: 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.