Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study extends earlier work on the role of vascular endothelial growth factor (VEGF) in the actions of antidepressant treatment in two key areas. First, by determining the requirement for VEGF in the actions of a 5-HT selective reuptake inhibitor (SSRI), fluoxetine in behavioral models of depression/antidepressant response; and second, by examining the role of the 5-HT1A receptor subtype in the regulation of VEGF, and the cellular localization of antidepressant regulation of VEGF expression. The results show that pharmacological inhibition of VEGF receptor signaling blocks the behavioral actions of fluoxetine in rats subjected to chronic unpredictable stress. Infusions of SU5416 or SU1498, two structurally dissimilar inhibitors of VEGF-Flk-1 receptor signaling, block the antidepressant effects of fluoxetine on sucrose preference, immobility in the forced swim test, and latency to feed in the novelty suppressed feeding paradigm. We also show that activation of 5-HT1A receptors is sufficient to induce VEGF expression and that a 5-HT1A antagonist blocks both the increase in VEGF and behavioral effects induced by fluoxetine. Finally, double labeling studies show that chronic fluoxetine administration increases VEGF expression in both neurons and endothelial cells in the hippocampus. Taken together these studies show that VEGF is necessary for the behavioral effects of the SSRI fluoxetine, as well as norepinephrine selective reuptake inhibitor, and that these effects may be mediated by 5-HT1A receptors located on neurons and endothelial cells.
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PMID:Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization. 1955 16

Aims: Serotonin 1A receptor (5-HT1A) and vascular endothelial growth factor (VEGF) are widely expressed in the neurons of the hippocampus and have significant roles in the pathophysiological processes of major depressive disorders (MDDs). The present study was designed to examine 5-HT1A and VEGF gene polymorphisms and whether the gene-gene interaction of 5-HT1A and VEGF gene variants was associated with MDD. Methods: A total of 264 MDD patients and 264 healthy controls were included in the present genetic study. The rs6295, rs1364043, and rs878567 single-nucleotide polymorphisms (SNPs) in the 5-HT1A gene and the rs699947, rs833061, and rs2010963 SNPs in the VEGF gene were selected for genotypic analyses. The generalized multifactor dimensionality reduction method was employed to assess their interactions. Results: The genotype distributions of the two genes' respective SNPs were significantly different between patients and controls for 5-HT1A rs6295 (p = 0.041) and VEGF rs2010963 (p = 0.035); however, no significant allelic variation in 5-HT1A (rs6295, rs1364043, and rs878567) and VEGF (rs699947, rs833061, and rs2010963) was found. The interactions between 5-HT1A (rs6295, rs1364043, and rs878567) and VEGF (rs699947, rs833061, and rs2010963) had a cross-validation (CV) consistency of 10/10 and a p value of 0.0107, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. Conclusions: The interactions between 5-HT1A and VEGF gene polymorphisms may play a key role in the development of MDD in the Northern Chinese Han population.
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PMID:Epistatic Interaction Between 5-HT1A and Vascular Endothelial Growth Factor Gene Polymorphisms in the Northern Chinese Han Population With Major Depressive Disorder. 3105 36