TITLE:
Kinetics of Norepinephrine- and Serotonin-Induced BDNF Release in Cultured Embryonic Hippocampal Neurons
AUTHORS:
Michael Chen, Amelia Russo-Neustadt
KEYWORDS:
BDNF; CREB; Serotonin; Norepinephrine; Hippocampus; Kinetics
JOURNAL NAME:
Neuroscience and Medicine,
Vol.4 No.4,
December
2,
2013
ABSTRACT: The primary neurotransmitters targeted
by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine,
which also are released in significant amounts in the central nervous system in
response to sympathetic nervous system activation. In cultured hippocampal
neurons, we have previously shown that norepinephrine induces increased expression
of brain-derived neurotrophic factor (BDNF), the PI-3 K/Akt, MAPK pro-survival pathways, the BDNF
receptor, TrkB, a transcription
factor, and cyclic AMP response element binding protein (CREB). In the present study, we
extend these findings of increased BDNF expression to its kinetics of release
into the surrounding media. We also evaluate these two cell survival pathways,
TrkB and CREB, in response to application of serotonin and/or norepinephrine. Serotonin
elicits an earlier, but brief expression and release of BDNF, whereas norepinephrine
elicits a more delayed and sustained release of BDNF. In response to both
norepinephrine and 5-HT, the presence of BDNF in lysates and subsequent release
into the media is significantly increased out to 4 h, as is PI-3 K/Akt activation. Together, these two
neurotransmitters increase BDNF expression and release covering the entire 8 h continuum evaluated. The results of this
study provide further evidence for a G protein-coupled receptor and a crosstalk-to-TrkB receptor with transactivation signaling across
pathways.