Document Detail


Rs6295 promoter variants of the serotonin type 1A receptor are differentially activated by c-Jun in vitro and correlate to transcript levels in human epileptic brain tissue.
MedLine Citation:
PMID:  23333373     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Many brain disorders, including epilepsy, migraine and depression, manifest with episodic symptoms that may last for various time intervals. Transient alterations of neuronal function such as related to serotonin homeostasis generally underlie this phenomenon. Several nucleotide polymorphisms (SNPs) in gene promoters associated with these diseases have been described. For obvious reasons, their regulatory roles on gene expression particularly in human brain tissue remain largely enigmatic. The rs6295 G-/C-allelic variant is located in the promoter region of the human HTR1a gene, encoding the G-protein-coupled receptor for 5-hydroxytryptamine (5HT1AR). In addition to reported transcriptional repressor binding, our bioinformatic analyses predicted a reduced binding affinity of the transcription factor (TF) c-Jun for the G-allele. In vitro luciferase transfection assays revealed c-Jun to (a) activate the rs6295 C- significantly stronger than the G-allelic variant and (b) antagonize efficiently the repressive effect of Hes5 on the promoter. The G-allele of rs6295 is known to be associated with aspects of major depression and migraine. In order to address a potential role of rs6295 variants in human brain tissue, we have isolated DNA and mRNA from fresh frozen hippocampal tissue of pharmacoresistant temporal lobe epilepsy (TLE) patients (n=140) after epilepsy surgery for seizure control. We carried out SNP genotyping studies and mRNA analyses in order to determine HTR1a mRNA expression in human hippocampal samples stratified according to the rs6295 allelic variant. The mRNA expression of HTR1a was significantly more abundant in hippocampal mRNA of TLE patients homozygous for the rs6295 C-allele as compared to those with the GG-genotype. These data may point to a novel, i.e. rs6295 allelic variant and c-Jun dependent transcriptional 5HT1AR 'receptoropathy'.
Authors:
Katharina Pernhorst; Karen M J van Loo; Marec von Lehe; Lutz Priebe; Sven Cichon; Stefan Herms; Per Hoffmann; Christoph Helmstaedter; Thomas Sander; Susanne Schoch; Albert J Becker
Related Documents :
22994453 - Inherent sex-dependent regulation of human hepatic cyp3a5.
23494473 - G protein-coupled estrogen receptor 1 expression in human vocal fold.
20367053 - Cytokine mrna expressions after racing at a high altitude and at sea level in horses wi...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  Brain research     Volume:  -     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier B.V.
Affiliation:
Depts. of Neuropathology, University of Bonn Medical Center.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Multimodal image analysis of sensorimotor gating in healthy women.
Next Document:  Electrophysiological evidence for the importance of interpersonal curiosity.