Document Detail


Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.
MedLine Citation:
PMID:  23323881     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region.
Authors:
A Akubuiro; M Bridget Zimmerman; L L Boles Ponto; S A Walsh; J Sunderland; L McCormick; M Singh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-18
Journal Detail:
Title:  Genes, brain, and behavior     Volume:  12     ISSN:  1601-183X     ISO Abbreviation:  Genes Brain Behav.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-09-23     Revised Date:  2014-03-25    
Medline Journal Info:
Nlm Unique ID:  101129617     Medline TA:  Genes Brain Behav     Country:  England    
Other Details:
Languages:  eng     Pagination:  311-22     Citation Subset:  IM    
Copyright Information:
Genes, Brain and Behavior © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Deaminase / genetics*,  metabolism
Animals
Biogenic Amines / metabolism
Corticotropin-Releasing Hormone / genetics,  metabolism
Diet, High-Fat
Eating
Feeding Behavior
Fluorodeoxyglucose F18
Glucose / metabolism
Goals
Hyperphagia / genetics,  metabolism,  physiopathology*
Hypothalamus / metabolism,  physiopathology*
Mice
Mice, Transgenic
Positron-Emission Tomography
Receptor, Serotonin, 5-HT2C / genetics,  metabolism
Receptors, Dopamine / genetics,  metabolism
Receptors, Opioid, mu / genetics,  metabolism
Reward
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
MH082234-02/MH/NIMH NIH HHS; R21 MH082234/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Biogenic Amines; 0/Receptor, Serotonin, 5-HT2C; 0/Receptors, Dopamine; 0/Receptors, Opioid, mu; 0Z5B2CJX4D/Fluorodeoxyglucose F18; 9015-71-8/Corticotropin-Releasing Hormone; EC 3.5.4.-/dsRNA adenosine deaminase; EC 3.5.4.4/Adenosine Deaminase; IY9XDZ35W2/Glucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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