Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine

Patrick C McHugh, Geraldine R Rogers, Barbara Loudon, Dylan M Glubb, Peter R Joyce, Martin A Kennedy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Antidepressant drugs can have significant effects on the mood of a patient suffering from major depression or other disorders. The pharmacological actions of these drugs generally affect the uptake or metabolism of the neurotransmitters serotonin, noradrenalin, and, to a lesser extent, dopamine. However, many aspects of antidepressant action are not understood. We conducted a proteomic analysis in a neuronal cell culture model in an attempt to identify molecules important to the operation of pathways functionally relevant to antidepressant action. The model involved generating cultures containing mixed neural and glial cells by controlled differentiation of mouse embryonic stem cells, followed by exposure to 1 microM paroxetine for 14 days. After antidepressant exposure, we observed increased expression or modification of sepiapterin reductase (SPR), heat shock protein 9A, RAS and EF-hand domain containing, and protein disulfide isomerase associated 3 and decreased expression or modification of creatine kinase, actin, prohibitin, a T-cell receptor alpha chain, defensin-related cryptdin 5, and the intermediate filament proteins glial fibrillary acidic protein and vimentin. SPR, the most strongly up-regulated protein observed, controls production of tetrahydrobiopterin, an essential cofactor for the synthesis of many neurotransmitters including serotonin, making it a plausible and intriguing candidate protein for involvement in mood control and antidepressant drug action. SPR and the other proteins identified may represent links to molecular processes of importance to mood dysregulation and control, and their respective genes may be novel candidates for the study of antidepressant pharmacogenetics.

LanguageEnglish
Pages306-16
Number of pages11
JournalJournal of Neuroscience Research
Volume86
Issue number2
DOIs
Publication statusPublished - 1 Feb 2008
Externally publishedYes

Fingerprint

Paroxetine
sepiapterin reductase
Embryonic Stem Cells
Proteomics
Antidepressive Agents
Neurotransmitter Agents
Serotonin
alpha-Defensins
Protein Disulfide-Isomerases
EF Hand Motifs
Antigen Receptors, T-Cell, alpha-beta
Intermediate Filament Proteins
Proteins
Glial Fibrillary Acidic Protein
Vimentin
Creatine Kinase
Heat-Shock Proteins
Neuroglia
Actins
Cell Differentiation

Cite this

McHugh, Patrick C ; Rogers, Geraldine R ; Loudon, Barbara ; Glubb, Dylan M ; Joyce, Peter R ; Kennedy, Martin A. / Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine. In: Journal of Neuroscience Research. 2008 ; Vol. 86, No. 2. pp. 306-16.
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Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine. / McHugh, Patrick C; Rogers, Geraldine R; Loudon, Barbara; Glubb, Dylan M; Joyce, Peter R; Kennedy, Martin A.

In: Journal of Neuroscience Research, Vol. 86, No. 2, 01.02.2008, p. 306-16.

Research output: Contribution to journalArticle

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T1 - Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine

AU - McHugh, Patrick C

AU - Rogers, Geraldine R

AU - Loudon, Barbara

AU - Glubb, Dylan M

AU - Joyce, Peter R

AU - Kennedy, Martin A

N1 - (c) 2007 Wiley-Liss, Inc.

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AB - Antidepressant drugs can have significant effects on the mood of a patient suffering from major depression or other disorders. The pharmacological actions of these drugs generally affect the uptake or metabolism of the neurotransmitters serotonin, noradrenalin, and, to a lesser extent, dopamine. However, many aspects of antidepressant action are not understood. We conducted a proteomic analysis in a neuronal cell culture model in an attempt to identify molecules important to the operation of pathways functionally relevant to antidepressant action. The model involved generating cultures containing mixed neural and glial cells by controlled differentiation of mouse embryonic stem cells, followed by exposure to 1 microM paroxetine for 14 days. After antidepressant exposure, we observed increased expression or modification of sepiapterin reductase (SPR), heat shock protein 9A, RAS and EF-hand domain containing, and protein disulfide isomerase associated 3 and decreased expression or modification of creatine kinase, actin, prohibitin, a T-cell receptor alpha chain, defensin-related cryptdin 5, and the intermediate filament proteins glial fibrillary acidic protein and vimentin. SPR, the most strongly up-regulated protein observed, controls production of tetrahydrobiopterin, an essential cofactor for the synthesis of many neurotransmitters including serotonin, making it a plausible and intriguing candidate protein for involvement in mood control and antidepressant drug action. SPR and the other proteins identified may represent links to molecular processes of importance to mood dysregulation and control, and their respective genes may be novel candidates for the study of antidepressant pharmacogenetics.

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KW - Image Processing, Computer-Assisted

KW - Mice

KW - Neurons/cytology

KW - Paroxetine/pharmacology

KW - Proteomics

KW - Reverse Transcriptase Polymerase Chain Reaction

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JO - Journal of Neuroscience Research

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