Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice

M Singh; M M Singh; E Na; Khristofor Agassandian; M B Zimmerman; A K Johnson

doi:10.1111/j.1601-183X.2011.00701.x

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Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice

Journal article

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Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice

M Singh, M M Singh, E Na, Khristofor Agassandian, M B Zimmerman and A K Johnson

Genes, brain and behavior, Vol.10(6), pp.637-647

08/2011

DOI: 10.1111/j.1601-183X.2011.00701.x

PMCID: PMC3150620

PMID: 21615684

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Abstract

Modulation of serotonin signaling by RNA editing of the serotonin 2C receptor (5HT(2C) R) may be relevant to affective disorder as serotonin functions regulate mood and behavior. Previously, we observed enhanced endogenous behavioral despair in ADAR2 transgenic mice. As the transcript of the 5HT(2C) R is a substrate of ADAR2, we hypothesized that perturbed ADAR2 equilibrium in the prefrontal cortex of ADAR2 transgenic mice alters the normal distribution of edited amino acid isoforms of the 5HT(2C) R and modifies the receptor function in downstream basal extracellular signal-regulated kinase (ERK) signaling. We examined groups of naive control and ADAR2 transgenic mice and found significantly increased ADAR2 expression, increased RNA editing at A, C, D and E sites and significantly altered normal distribution of edited amino acid isoforms of the 5HT(2C) R with increased proportions of valine asparagine valine, valine serine valine, valine asparagine isoleucine, isoleucine asparagine valine and decreased isoleucine asparagine isoleucine amino acid isoforms of the 5HT(2C) R in ADAR2 transgenic mice. Localized serotonin levels (5-HT) were unchanged and perturbed ADAR2 equilibrium coincides with dysregulated edited amino acid isoforms of the 5HT(2C) R and reduced basal ERK signaling. These results altogether suggest that altered 5HT(2C) R function could be contributing to enhanced depression-like behavior of ADAR2 transgenic mice and further implicate ADAR2 as a contributing factor in cases of affective disorder.

Adenosine Deaminase - genetics

Adenosine Deaminase - metabolism

RNA Editing - genetics

RNA, Messenger - genetics

Receptor, Serotonin, 5-HT2C - metabolism

Behavior, Animal - physiology

Mice, Transgenic

RNA-Binding Proteins

Depression - genetics

RNA, Messenger - metabolism

Animals

Prefrontal Cortex - metabolism

Mice

Receptor, Serotonin, 5-HT2C - genetics

Details

Title: Subtitle: Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice
Creators: M Singh - Department of Internal Medicine, University of Iowa, Iowa City, USA. minati-singh@uiowa.edu
M M Singh
E Na
Khristofor Agassandian
M B Zimmerman
A K Johnson
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.10(6), pp.637-647
Publisher: England
DOI: 10.1111/j.1601-183X.2011.00701.x
PMID: 21615684
PMCID: PMC3150620
ISSN: 1601-1848
eISSN: 1601-183X
Grant note: R01 DK066086 / NIDDK NIH HHS MH082234-02 / NIMH NIH HHS R01 MH080241 / NIMH NIH HHS R21 MH082234 / NIMH NIH HHS P01 HL014388 / NHLBI NIH HHS R21 MH082234-01A1 / NIMH NIH HHS DK-66086 / NIDDK NIH HHS HL-14388 / NHLBI NIH HHS
Language: English
Date published: 08/2011
Academic Unit: Psychological and Brain Sciences; Biostatistics; Neuroscience and Pharmacology; Health and Human Physiology; Internal Medicine
Record Identifier: 9983997470102771

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