title: A method for biomarker measurements in peripheral blood mononuclear cells isolated from anxious and depressed mice: β-arrestin 1 protein levels in depression and treatment.
abstract: A limited number of biomarkers in the central and peripheral systems which are known may be useful for diagnosing major depressive disorders and predicting the effectiveness of antidepressant (AD) treatments. Since 60% of depressed patients do not respond adequately to medication or are resistant to ADs, it is imperative to delineate more accurate biomarkers. Recent clinical studies suggest that β-arrestin 1 levels in human mononuclear leukocytes may be an efficient biomarker. If potential biomarkers such as β-arrestin 1 could be assessed from a source such as peripheral blood cells, then they could be easily monitored and used to predict therapeutic responses. However, no previous studies have measured β-arrestin 1 levels in peripheral blood mononuclear cells (PBMCs) in anxious/depressive rodents. This study aimed to develop a method to detect β-arrestin protein levels through immunoblot analyses of mouse PBMCs isolated from whole blood. In order to validate the approach, β-arrestin levels were then compared in na\"{\i}ve, anxious/depressed mice, and anxious/depressed mice treated with a selective serotonin reuptake inhibitor (fluoxetine, 18~mg/kg/day in the drinking water). The results demonstrated that mouse whole blood collected by submandibular bleeding permitted isolation of enough PBMCs to assess circulating proteins such as β-arrestin 1. β-Arrestin 1 levels were successfully measured in healthy human subject and na\"{\i}ve mouse PBMCs. Interestingly, PBMCs from anxious/depressed mice showed significantly reduced β-arrestin 1 levels. These decreased β-arrestin 1 expression levels were restored to normal levels with chronic fluoxetine treatment. The results suggest that isolation of PBMCs from mice by submandibular bleeding is a useful technique to screen putative biomarkers of the pathophysiology of mood disorders and the response to ADs. In addition, these results confirm that β-arrestin 1 is a potential biomarker for depression.
authors.affiliation: EA3544, Faculté de Pharmacie, Université Paris-Sud Châtenay-Malabry, France.
authors.forename: Indira
authors.initials: I
authors.lastname: Mendez-David
authors.forename: Zeina
authors.initials: Z
authors.lastname: El-Ali
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.forename: Bruno
authors.initials: B
authors.lastname: Falissard
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Corruble
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.forename: Saadia
authors.initials: S
authors.lastname: Kerdine-Römer
authors.forename: Denis J
authors.initials: DJ
authors.lastname: David
keywords: \boldsymbolβ-arrestin 1; anxiety; biomarkers; depression; fluoxetine; mouse models; peripheral blood mononuclear cells