Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression

Lucia Carboni; Serena Becchi; Chiara Piubelli; Alessandra Mallei; Roberto Giambelli; Maria Razzoli; Aleksander A. Mathé; Maurizio Popoli; Enrico Domenici

doi:10.1016/j.pnpbp.2010.05.019

Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression

Lucia Carboni, Serena Becchi, Chiara Piubelli, Alessandra Mallei, Roberto Giambelli, Maria Razzoli, Aleksander A. Mathé, Maurizio Popoli, Enrico Domenici

Integrative Biology and Physiology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

Background: Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins. Methods: Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays. Results: Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, α1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1α and BDNF. CRP levels were significantly reduced.The impact of early-life stress was assessed by comparing FSL. +. MS versus FSL. Apo-E, α1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated.The effect of stress in antidepressant response was then evaluated. In the comparison FSL. +. ESC. +. MS versus FSL. +. ESC, albumin, α1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL. +. NOR. +. MS versus FSL. +. NOR proteins like Apo-AIV, pyruvate dehydrogenase, α1-macroglobulin, transferrin and complement-C3 showed different levels. Conclusions: Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.

Original language	English (US)
Pages (from-to)	1037-1048
Number of pages	12
Journal	Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume	34
Issue number	6
DOIs	https://doi.org/10.1016/j.pnpbp.2010.05.019
State	Published - Aug 2010

Bibliographical note

Funding Information:
The authors wish to thank Weronica Andersson for technical support with the maternal separation procedure. This work was part of a project funded by the European Commission that combined large-scale clinical pharmacogenomic studies on depressed patients with preclinical investigations on animal models of disease, focusing on treatment with proserotonergic and pronoradrenergic antidepressants, called “Genome-based therapeutic drugs for depression (GENDEP)”, contract number LSHB-CT-2003-503428 . This work was also supported by the Swedish Medical Research Council grant 10414 (AAM).

Keywords

Antidepressant
Biomarkers
Flinders Sensitive Line
Maternal separation
Proteomics

Access

10.1016/j.pnpbp.2010.05.019

OpenUrl availability

Full text

Cite this

Carboni, L., Becchi, S., Piubelli, C., Mallei, A., Giambelli, R., Razzoli, M., Mathé, A. A., Popoli, M., & Domenici, E. (2010). Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34(6), 1037-1048. https://doi.org/10.1016/j.pnpbp.2010.05.019

Carboni, L, Becchi, S, Piubelli, C, Mallei, A, Giambelli, R, Razzoli, M, Mathé, AA, Popoli, M & Domenici, E 2010, 'Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 34, no. 6, pp. 1037-1048. https://doi.org/10.1016/j.pnpbp.2010.05.019

@article{13b9cbb3df2543d983858795f89c12df,

title = "Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression",

abstract = "Background: Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins. Methods: Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays. Results: Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, α1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1α and BDNF. CRP levels were significantly reduced.The impact of early-life stress was assessed by comparing FSL. +. MS versus FSL. Apo-E, α1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated.The effect of stress in antidepressant response was then evaluated. In the comparison FSL. +. ESC. +. MS versus FSL. +. ESC, albumin, α1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL. +. NOR. +. MS versus FSL. +. NOR proteins like Apo-AIV, pyruvate dehydrogenase, α1-macroglobulin, transferrin and complement-C3 showed different levels. Conclusions: Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.",

keywords = "Antidepressant, Biomarkers, Flinders Sensitive Line, Maternal separation, Proteomics",

author = "Lucia Carboni and Serena Becchi and Chiara Piubelli and Alessandra Mallei and Roberto Giambelli and Maria Razzoli and Math{\'e}, {Aleksander A.} and Maurizio Popoli and Enrico Domenici",

note = "Funding Information: The authors wish to thank Weronica Andersson for technical support with the maternal separation procedure. This work was part of a project funded by the European Commission that combined large-scale clinical pharmacogenomic studies on depressed patients with preclinical investigations on animal models of disease, focusing on treatment with proserotonergic and pronoradrenergic antidepressants, called “Genome-based therapeutic drugs for depression (GENDEP)”, contract number LSHB-CT-2003-503428 . This work was also supported by the Swedish Medical Research Council grant 10414 (AAM).",

year = "2010",

month = aug,

doi = "10.1016/j.pnpbp.2010.05.019",

language = "English (US)",

volume = "34",

pages = "1037--1048",

journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",

issn = "0278-5846",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression

AU - Carboni, Lucia

AU - Becchi, Serena

AU - Piubelli, Chiara

AU - Mallei, Alessandra

AU - Giambelli, Roberto

AU - Razzoli, Maria

AU - Mathé, Aleksander A.

AU - Popoli, Maurizio

AU - Domenici, Enrico

N1 - Funding Information: The authors wish to thank Weronica Andersson for technical support with the maternal separation procedure. This work was part of a project funded by the European Commission that combined large-scale clinical pharmacogenomic studies on depressed patients with preclinical investigations on animal models of disease, focusing on treatment with proserotonergic and pronoradrenergic antidepressants, called “Genome-based therapeutic drugs for depression (GENDEP)”, contract number LSHB-CT-2003-503428 . This work was also supported by the Swedish Medical Research Council grant 10414 (AAM).

PY - 2010/8

Y1 - 2010/8

N2 - Background: Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins. Methods: Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays. Results: Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, α1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1α and BDNF. CRP levels were significantly reduced.The impact of early-life stress was assessed by comparing FSL. +. MS versus FSL. Apo-E, α1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated.The effect of stress in antidepressant response was then evaluated. In the comparison FSL. +. ESC. +. MS versus FSL. +. ESC, albumin, α1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL. +. NOR. +. MS versus FSL. +. NOR proteins like Apo-AIV, pyruvate dehydrogenase, α1-macroglobulin, transferrin and complement-C3 showed different levels. Conclusions: Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.

AB - Background: Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins. Methods: Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays. Results: Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, α1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1α and BDNF. CRP levels were significantly reduced.The impact of early-life stress was assessed by comparing FSL. +. MS versus FSL. Apo-E, α1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated.The effect of stress in antidepressant response was then evaluated. In the comparison FSL. +. ESC. +. MS versus FSL. +. ESC, albumin, α1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL. +. NOR. +. MS versus FSL. +. NOR proteins like Apo-AIV, pyruvate dehydrogenase, α1-macroglobulin, transferrin and complement-C3 showed different levels. Conclusions: Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.

KW - Antidepressant

KW - Biomarkers

KW - Flinders Sensitive Line

KW - Maternal separation

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=77955054324&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955054324&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2010.05.019

DO - 10.1016/j.pnpbp.2010.05.019

M3 - Article

C2 - 20580919

AN - SCOPUS:77955054324

SN - 0278-5846

VL - 34

SP - 1037

EP - 1048

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

IS - 6

ER -

Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this