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Region-specific regulation of the serotonin 2A receptor expression in development and aging in postmortem human brain


Marinova, Zoya; Monoranu, Camelia-Maria; Fetz, Sonja; Walitza, Susanne; Grünblatt, Edna (2015). Region-specific regulation of the serotonin 2A receptor expression in development and aging in postmortem human brain. Neuropathology and Applied Neurobiology, 41(4):520-532.

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.
METHODS
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.

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.
METHODS
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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
04 Faculty of Medicine > Neuroscience Center Zurich
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2015
Deposited On:23 Jul 2014 08:48
Last Modified:05 Apr 2016 17:59
Publisher:Wiley-Blackwell
ISSN:0305-1846
Additional Information:This is the accepted version of the following article: Neuropathology and Applied Neurobiology 2014: Epub ahead of print, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/nan.12167/abstract.
Publisher DOI:https://doi.org/10.1111/nan.12167
PubMed ID:25041420

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