Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice.
Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice.
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DOI：
10.1111/j.1601-183x.2011.00701.x
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发表时间：
2011-08
期刊：
影响因子：
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通讯作者：
Johnson AK
中科院分区：
文献类型：
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作者：
Singh M;Singh MM;Na E;Agassandian K;Zimmerman MB;Johnson AK
Modulation of serotonin signaling by RNA editing of the serotonin 2C receptor (5HT2CR) may be relevant to affective disorder as serotonin functions regulate mood and behavior. Previously we observed enhanced endogenous behavioral despair in ADAR2 transgenic mice. Since the transcript of the 5HT2CR 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 5HT2CR and modifies the receptor function in downstream basal ERK signaling. We examined groups of naïve 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 5HT2CR with increased proportions of VNV, VSV, VNI, INV and decreased INI amino acid isoforms of the 5HT2CR in ADAR2 transgenic mice. Localized serotonin levels (5-HT) were unchanged and perturbed ADAR2 equilibrium coincides with dysregulated edited amino acid isoforms of the 5HT2CR and reduced basal ERK signaling. These results altogether suggest that altered 5HT2CR 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.
