The function of Notch1 signaling was increased in parallel with neurogenesis in rat hippocampus after chronic fluoxetine administration.
Chronic fluoxetine administration can increase neurogenesis in the adult hippocampus, but the molecular mechanisms remain unclear. The Notch1 signaling pathway is expressed highly in the hippocampus and could be a target for diverse environmental modulators of adult neurogenesis. This prompted us to investigate whether the effect of fluoxetine on hippocampal neurogenesis involves Notch1 signaling. In this study, the function of Notch1 signaling was investigated by real time polymerase chain reaction (PCR) and Western blot at different time points (14 d or 28 d) after fluoxetine administration. Simultaneously, hippocampal neurogenesis was determined by assessing cell proliferation, survival and differentiation. mRNA and protein expression of Notch1 signaling components (including Jag1, NICD, Hes1 and Hes5) in the hippocampus increased after fluoxetine administration, accompanied by cell proliferation and survival. These results indicate that chronic fluoxetine administration activates Notch1 signaling in the hippocampus, and the up-regulation of the Notch1 pathway brought about by chronic fluoxetine administration might partly contribute to increased neurogenesis in hippocampus. The findings may provide new insights into the regulatory mechanisms of neurogenesis induced by fluoxetine.
School of Clinical Medicine, Southeast University, Nanjing, China.
Yuxiu
Y
Sui
Zhijun
Z
Zhang
Yijing
Y
Guo
Yi
Y
Sun
Xiaobing
X
Zhang
Chunming
C
Xie
Yuan
Y
Li
Guangjun
G
Xi
D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000187:drug effects* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D005473:Fluoxetine; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D012097:Repressor Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C489686:Hes5 protein, rat; C000606275:Jag1 protein, rat; C497763:Notch1 protein, rat