β-Arrestin-1 Levels: Reduced in Leukocytes of Patients With Depression and Elevated by Antidepressants in Rat Brain

Abstract

The findings in the rat study suggest beta-arrestin-1 elevation as a biochemical mechanism for antidepressant-induced receptor down-regulation. The findings in human subjects support the implication of beta-arrestin-1 in the pathophysiology of mood disorders. Beta-arrestin-1 measurements in patients with depression may potentially serve as a biochemical marker for depression.

Non-Response to Initial Antidepressant Therapy

“…A substantial body of evidence has accumulated indicating that β-arrestins play a major role in the pathophysiology of mood disorders, as well as in the mechanisms of action of antidepressants. In human, for example, changes in β-arrestins expression are detected in MD patients and in response to stress while various antidepressant drugs reverse these changes (Avissar et al, 2004). Overall, these data suggest that β-arrestins could be major molecular determinants of the effects of fluoxetine, and, more generally, of SSRIs and SNRIs.…”

“…Overall, these data suggest that β-arrestins could be major molecular determinants of the effects of fluoxetine, and, more generally, of SSRIs and SNRIs. β-arrestin-1 protein and mRNA levels in mononuclear leukocytes of untreated patients with MD are significantly lower than those of healthy subjects and these levels are significantly correlated with the severity of depressive symptomatology (Avissar et al, 2004;Schreiber et al, 2009). The low β-arrestin-1 protein and mRNA levels were alleviated by antidepressant treatments, whereby normalization of β-arrestin-1 preceded, and thus predicted, clinical improvement.…”

Antidepressants Increase β-Arrestin2 Ubiquitinylation and Degradation by the Proteasomal Pathway in C6Rat Glioma Cells

“…Cytosolic and membrane fractions were thawed on the day of assay. Protein aliquots (30 g/lane) were taken for protein separation by SDS-polyacrylamide gel electrophoresis as described previously (Avissar et al, 2004). Semiquantitative analysis was performed using a computerized image analysis system (EZQuant-Gel 2.11; EZQuant Biology Software Solutions Ltd., Tel Aviv, Israel).…”

“…␤-Arrestin1 protein and mRNA levels in mononuclear leukocytes of yet untreated patients with major depression were significantly lower than those of healthy subjects and correlated with the severity of depressive symptomatology (Avissar et al, 2004;MatuzanyRuban et al, 2005). The low ␤-arrestin1 measures were alleviated by antidepressant treatment within 1 to 3 weeks (Matuzany-Ruban et al, 2005).…”

GRK et arrestines : la piste thérapeutique ?

“…Par ailleurs, une augmentation de l'arrestine 2 est observée dans le cortex et l'hippocampe de rats sous traitement antidépresseur. Chez l'homme, l'expression de l'arrestine 2 dans les cellules mononuclées du sang est inversement corrélée à la sévérité de la dépression [22], la normalisation de son taux précédant l'améliora- tion des signes cliniques de la maladie [23]. L'ensemble de ces résultats suggère un lien probable entre les récepteurs α 2A -adrénergiques et la GRK2 chez les sujets atteints de dépression majeure, et souligne le rôle de la GRK2 et de l'arrestine 2 comme marqueurs biochimiques potentiels dans la réponse au traitement.…”