5-HT1A receptor expression : Studies in postmortem tissue and characterisation of a model system.
type: CreativeWork
description: Serotonin (5-HT) neurotransmission is involved in the psychopharmacology of several psychiatric disorders including, depression, anxiety disorders and schizophrenia. The release of 5-HT in neurons is mediated by somatodendritic 5-HT[1A] autoreceptors. The presence of 5-HT[1A] receptor is thought to be increased in depressed patients, producing a reduction in the synthesis of 5-HT. A common single nucleotide polymorphism in the promoter region of 5HT[1A] receptor C-1019G is also associated with depression and suicide. The nuclear DEAF-1 related (NUDR) protein represses the 5-HT[1A] promoter region hence regulating both 5-HT[1A] transcription and receptor expression. The project involved undertaking a post-mortem study to determine any association between the 5-HT[1A] promoter polymorphism and the expression of 5-HT[1A] receptor mRNA and receptor density in control human hippocampal brain tissue. This was achieved by genotyping human brain tissue for the 5-HT[1A] receptor polymorphism C-1019G and 5-HT[1A] receptor mRNA levels were quantified using real-time PCR. Radioligand binding was used to determine B[max] and Kd quantifying 5-HT[1A] receptor density. The SHSY-5Y neuroblastoma cell line is a well characterised cell line model used in neurotransmitter studies when differentiated. The 5-HT[1A] receptor couples to Gi proteins inhibiting AC activity and hence mediating a variety of intracellular changes such as, decreasing cAMP leading to decreased Ca[2+] levels. The SH-SY5Y cell line study investigated whether the 5-HT[1A] agonist 8-OH-DPAT, inhibited forskolin stimulated Ca[2+] release in the SHSY-5Y cell line and whether the 5-HT[1A] antagonist p-MPPI reversed this effect using flow cytometry. The post-mortem study showed that the G-1019 allele had significantly higher 5-HT[1A] expression compared to the C allele in control hippocampal tissue. Radioligand binding data demonstrated that control samples with a GG or G/C genotype had a significantly higher 5-HT[1A] re…
abstract: Serotonin (5-HT) neurotransmission is involved in the psychopharmacology of several psychiatric disorders including, depression, anxiety disorders and schizophrenia. The release of 5-HT in neurons is mediated by somatodendritic 5-HT[1A] autoreceptors. The presence of 5-HT[1A] receptor is thought to be increased in depressed patients, producing a reduction in the synthesis of 5-HT. A common single nucleotide polymorphism in the promoter region of 5HT[1A] receptor C-1019G is also associated with depression and suicide. The nuclear DEAF-1 related (NUDR) protein represses the 5-HT[1A] promoter region hence regulating both 5-HT[1A] transcription and receptor expression. The project involved undertaking a post-mortem study to determine any association between the 5-HT[1A] promoter polymorphism and the expression of 5-HT[1A] receptor mRNA and receptor density in control human hippocampal brain tissue. This was achieved by genotyping human brain tissue for the 5-HT[1A] receptor polymorphism C-1019G and 5-HT[1A] receptor mRNA levels were quantified using real-time PCR. Radioligand binding was used to determine B[max] and Kd quantifying 5-HT[1A] receptor density. The SHSY-5Y neuroblastoma cell line is a well characterised cell line model used in neurotransmitter studies when differentiated. The 5-HT[1A] receptor couples to Gi proteins inhibiting AC activity and hence mediating a variety of intracellular changes such as, decreasing cAMP leading to decreased Ca[2+] levels. The SH-SY5Y cell line study investigated whether the 5-HT[1A] agonist 8-OH-DPAT, inhibited forskolin stimulated Ca[2+] release in the SHSY-5Y cell line and whether the 5-HT[1A] antagonist p-MPPI reversed this effect using flow cytometry. The post-mortem study showed that the G-1019 allele had significantly higher 5-HT[1A] expression compared to the C allele in control hippocampal tissue. Radioligand binding data demonstrated that control samples with a GG or G/C genotype had a significantly higher 5-HT[1A] re…
author: Bunn, Lindsey J.
language: en
date published: 2008
date modified: 2026-07-24T06:31:14Z
provider: Sheffield Hallam University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Sheffield Hallam University (United Kingdom).