Altered ADAR 2 equilibrium and 5HT2CR editing in the prefrontal cortex of ADAR 2 transgenic mice
| Autor: | Alan Kim Johnson, K. Agassandian, M. B. Zimmerman, Minati Singh, M. M. Singh, Elisa S. Na |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Adenosine Deaminase Prefrontal Cortex Mice Transgenic Biology Article Serine Mice Behavioral Neuroscience Valine Internal medicine Receptor Serotonin 5-HT2C Genetics medicine Animals RNA Messenger Asparagine chemistry.chemical_classification Behavior Animal Depression RNA-Binding Proteins Cell biology Amino acid Endocrinology Neurology chemistry RNA editing ADAR RNA Editing Serotonin Isoleucine |
| Zdroj: | Genes, Brain and Behavior. 10:637-647 |
| ISSN: | 1601-1848 |
| DOI: | 10.1111/j.1601-183x.2011.00701.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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