Dynamics of beta-arrestin1 protein and mRNA levels elevation by antidepressants in mononuclear leukocytes of patients with depression.
BACKGROUND
Beta-arrestins interfere in G protein-receptor interaction leading to desensitization of G protein-mediated receptor signaling. G protein-receptor signaling and its desensitization were previously implicated in the pathophysiology, diagnosis and treatment of mood disorders. The present study aims at evaluating alterations in beta-arrestin1 protein and mRNA levels in mononuclear leukocytes of untreated patients with major depression and the effects and time course of antidepressant treatments on these alterations.


METHODS
Repeated beta-arrestin1 protein and mRNA measurements, through immunoblot analyses using monoclonal antibodies against beta-arrestin1 and reverse transcriptase polymerase chain reaction, respectively, were carried in mononuclear leukocytes of 18 patients with major depression and compared with 18 healthy subjects. Each patient was examined while untreated and after 1, 2, and 4 weeks of antidepressant treatment.


RESULTS
Beta-arrestin1 protein and mRNA levels in mononuclear leukocytes of untreated patients with major depression were significantly lower than those of healthy subjects. The low beta-arrestin1 protein and mRNA levels were alleviated by antidepressant treatment. Normalization of beta-arrestin1 measures preceded, and thus predicted clinical improvement.


CONCLUSIONS
These findings support the implication of beta-arrestin1 in the pathophysiology of major depression and in the mechanism underlying antidepressant-induced receptor down-regulation and therapeutic effects. Beta-arrestin1 measurements in patients with depression may potentially serve for biochemical diagnostic purposes and for monitoring and predicting response to antidepressants.
Matuzany-Ruban
A
A
Department of Pharmacology, Faculty for Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel.
Avissar
S
S
Schreiber
G
G
D000328:Adult; D019390:Arrestins / Q000032:analysis / Q000096:biosynthesis*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071557:beta-Arrestins
D019390:Arrestins; D012333:RNA, Messenger; D000071557:beta-Arrestins