Region-Specific Regulation of the Serotonin 2a Receptor Expression in Development and Aging in Postmortem Human Brain

Abstract

AIMS The serotonin 2A receptor (HTR2A) is widely expressed in the brain and involved in the modulation of fear, mood, anxiety and other symptoms. HTR2A and HTR2A gene variations are implicated in depression, schizophrenia, anxiety and obsessive-compulsive disorder. To understand HTR2A signalling changes in psychiatric or neurodegenerative disorders, its normal pattern of brain expression and region specificity during development and aging needs to be clarified. The aim of the present study was to assess HTR2A expression through developmental and aging stages in six brain regions in postmortem human brain samples from individuals with no clinical or neuropathological evidence of neuropsychiatric disorders and to investigate the interaction with the rs6311 HTR2A promoter polymorphism. METH-ODS DNA, RNA and protein were isolated from postmortem brain samples including six regions (frontal cortex, striatum, amygdala, thalamus, brain stem and cerebellum) from 55 individuals. HTR2A mRNA levels were assessed using quantitative real time RT-PCR, and HTR2A protein levels -with western blot. The rs6311 HTR2A polymorphism was analyzed with genotyping. RESULTS We found that HTR2A mRNA and protein levels are differentially regulated with age in different brain regions studied, but are not affected by gender. Significant changes in HTR2A expression with age were found in frontal cortex, amygdala, thalamus, brain stem, and cerebellum. CONCLUSIONS Our results show plasticity and region specificity of HTR2A expression regulation in human brain with age, which may be important for the interaction with other neurotransmitter systems and for the occurrence of developmental periods with increased vulnerability to neuropsychiatric or neurodegenerative disorders. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nan.12167 Accepted ArticleThis article is protected by copyright. All rights reserved. Significant changes in HTR2A expression with age were found in frontal cortex, amygdala, thalamus, brain stem, and cerebellum. Conclusions: Our results show plasticity and region specificity of HTR2A expression regulation in human brain with age, which may be important for the interaction with other neurotransmitter systems and for the occurrence of developmental periods with increased vulnerability to neuropsychiatric or neurodegenerative disorders.