AUTHOR=MENDEZ-DAVID Indira , EL-ALI Zeina , HEN Rene , FALISSARD Bruno , CORRUBLE Emmanuelle , GARDIER Alain M., KERDINE-ROMER Saadia , DAVID Denis J.

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 4 - 2013

YEAR=2013

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2013.00124

DOI=10.3389/fphar.2013.00124

ISSN=1663-9812

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 treatments. Since 60% of depressed patients do not respond adequately to medication or are resistant to antidepressants, 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 naïve, anxious/depressed mice, and anxious/depressed mice treated treated with a selective serotonin reuptake inhibitor (SSRI; 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 naïve 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 antidepressants. In addition, these results confirm that β-arrestin 1 is a potential biomarker for depression.