Altered RNA editing of serotonin 2C receptor in a rat model of depression.
Altered RNA editing of serotonin 2C receptor (HTR2C) has been suggested to be involved in the pathophysiology of major depression. Here we examined RNA editing status of HTR2C in the learned helplessness (LH) rats, one of well-established animal models of depression. LH rats showed the significantly increased RNA editing of site E, and tendency for increased RNA editing of other editing sites. Treatment with fluoxetine, a selective serotonin reuptake inhibitor, or imipramine, a tricyclic antidepressant, affected the RNA editing status of the LH rats. Although, these antidepressants differentially altered RNA editing status, they commonly reduced RNA editing efficiency of site E. We further revealed that altered RNA editing in the LH rats and by antidepressants was not explained by altered expression of RNA editing enzymes or their substrates (adenosine deaminases that act on RNA, HTR2C, and spliced form of HTR2C). These results suggest that alteration of RNA editing of HTR2C may play a role in the pathophysiology of depression and action of antidepressants.
Iwamoto
Kazuya
K
Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako city, Saitama 351 0198, Japan. kaziwamoto@brain.riken.go.jp
Nakatani
Noriaki
N
Bundo
Miki
M
Yoshikawa
Takeo
T
Kato
Tadafumi
T
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D003001:Cloning, Molecular; D003863:Depression / Q000188:drug therapy / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D014644:Genetic Variation / Q000502:physiology; D006380:Helplessness, Learned; D008297:Male; D017393:RNA Editing; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017421:Sequence Analysis / Q000379:methods
D000928:Antidepressive Agents; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase