PMID- 17915260 OWN - NLM STAT- MEDLINE DCOM- 20071126 LR - 20211020 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 81 IP - 16 DP - 2007 Sep 29 TI - Nitric oxide signaling participates in norepinephrine-induced activity of neuronal intracellular survival pathways. PG - 1280-90 AB - Much evidence has gathered that nitric oxide (NO) signaling, via cGMP-dependent mechanisms, may activate pro-survival pathways in hippocampal neurons and inhibit apoptosis. Past research has revealed that the enhancement of monoaminergic neurotransmission via exercise or treatment with antidepressant medications leads to an enhanced expression of brain-derived neurotrophic factor (BDNF). In isolated hippocampal neurons, norepinephrine (NE) application also increases the immunoreactivity of BDNF and several pro-survival signaling molecules. The data herein support the possibility that NO signaling plays an important role in enhancing neurotrophin expression and activation of the pro-survival phosphatidylinositol 3' kinase (PI-3K) pathway stimulated by NE. In isolated hippocampal neurons, the NO donor, sodium nitroprusside, increases BDNF, PI-3K, and phospho-ERK1 immunoreactivity. Specific inhibitors of the NO system suggest that NE-induced increases in hippocampal BDNF and the PI-3K pathway, but not stimulation of the MAPK pathway, depend upon NO signaling. In addition, inhibiting cGMP suggest that the effects of NE on BDNF immunoreactivity and Akt phosphorylation are also cGMP-dependent. Finally, the application of l-NAME to hippocampal neurons increases cell death. This is the first study of its kind demonstrating the involvement of NE-induced pro-survival signaling in three distinct signaling pathways: PI-3K, MAPK, and NO/cGMP. Possible mechanisms are discussed in light of the results. FAU - Chen, Michael J AU - Chen MJ AD - Department of Biological Sciences, California State University, 5151 State University Drive, Los Angeles, CA 90032, USA. mjchen@calstatela.edu FAU - Russo-Neustadt, Amelia A AU - Russo-Neustadt AA LA - eng GR - R01 MH059776/MH/NIMH NIH HHS/United States GR - R01 MH059776-10/MH/NIMH NIH HHS/United States GR - MH 59776/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070915 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Nitric Oxide Donors) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 4.6.1.2 (Guanylate Cyclase) RN - H2D2X058MU (Cyclic GMP) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cyclic GMP/metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Enzyme Inhibitors/pharmacology MH - Female MH - Gestational Age MH - Guanylate Cyclase/antagonists & inhibitors MH - *Hippocampus/cytology/embryology/metabolism MH - Mitogen-Activated Protein Kinase Kinases/metabolism MH - *Neurons/cytology/drug effects/metabolism MH - Nitric Oxide/*metabolism MH - Nitric Oxide Donors/pharmacology MH - Nitric Oxide Synthase/antagonists & inhibitors MH - Norepinephrine/*pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Rats MH - Signal Transduction PMC - PMC2435382 MID - NIHMS32991 EDAT- 2007/10/05 09:00 MHDA- 2007/12/06 09:00 PMCR- 2008/06/23 CRDT- 2007/10/05 09:00 PHST- 2007/06/27 00:00 [received] PHST- 2007/08/08 00:00 [revised] PHST- 2007/09/05 00:00 [accepted] PHST- 2007/10/05 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2007/10/05 09:00 [entrez] PHST- 2008/06/23 00:00 [pmc-release] AID - S0024-3205(07)00664-9 [pii] AID - 10.1016/j.lfs.2007.09.003 [doi] PST - ppublish SO - Life Sci. 2007 Sep 29;81(16):1280-90. doi: 10.1016/j.lfs.2007.09.003. Epub 2007 Sep 15.