Involvement of vascular endothelial growth factor in serotonin 1A receptor-mediated neuroproliferation in neonatal mouse hippocampus.

The serotonin 1A receptor (5-HT1A-R) has been linked to many diverse functions in the brain. Our earlier studies have revealed its signaling pathways and function in the hippocampus as well as the prefrontal cortex of neonatal and young adult mice of two strains, C57BL6 and Swiss Webster. Such experiments have revealed that the 5-HT1A-R associates and functionally cooperates with molecules like calmodulin kinase II and the N-methyl-d-aspartic acid receptor to stimulate clozapine-evoked neuronal activity in the prefrontal cortex. Furthermore, in the neonatal mouse brain, 5-HT1A-R signaling plays a profound role in orchestrating hippocampal development through protein kinase C isozymes and the extracellular signal-regulated kinases 1 and 2 (ERK1/2). Results presented here establish that downstream of ERK1/2, vascular endothelial growth factor (VEGF) signaling further amplifies the ERK1/2-mediated neuroproliferative signaling in the neonatal hippocampus. This also indicates that VEGF signaling inhibitors, typically used in cancer therapy, may cause serious detrimental effects by inhibiting hippocampal neuroproliferation.