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Antidepressants elevate GDNF expression and release from C6 glioma cells in a β-arrestin1-dependent, CREB interactive pathway.
MedLine Citation:
PMID:  21223624     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Glial cell line-derived neurotrophic factor (GDNF), essential for neuronal survival, plasticity and development, has been implicated in the mechanism of action of antidepressant drugs (ADs). β-arrestin1, a member of the arrestin protein family, was found to play a role in AD mechanism of action. The present study aimed at evaluating whether the effect of ADs on GDNF in C6 rat glioma cells is exerted through a β-arrestin1-dependent, CREB-interactive pathway. For chronic treatment, C6 rat glioma cells were treated for 3 d with different classes of ADs: imipramine – a non-selective monoamine reuptake inhibitor, citalopram – a serotonin selective reuptake inhibitor (SSRI) or desipramine – a norepinephrine selective reuptake inhibitor (NSRI) and compared to mood stabilizers (lithium and valproic acid) or to the antipsychotic haloperidol. Only ADs significantly elevated β-arrestin1 levels in the cytosol, while reducing phospho-β-arrestin1 levels in the cell nuclear fraction. ADs significantly increased both GDNF expression and release from the cells, but were unable to induce such effects in β-arrestin1 knock-down cells. Chronic AD treatment significantly increased CREB phosphorylation without altering the level of total CREB in the nuclear fraction of the cells. Moreover, treatment with ADs significantly increased β-arrestin1/CREB interaction. These findings support the involvement of β-arrestin1 in the mechanism of action of ADs. We suggest that following AD treatment, β-arrestin1 generates a transcription complex involving CREB essential for GDNF expression and release, thus enhancing GDNF's neuroprotective action that promotes cellular survival and plasticity when the survival and function of neurons is compromised as occurs in major depression.
Authors:
Moran Golan; Gabriel Schreiber; Sofia Avissar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-12
Journal Detail:
Title:  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)     Volume:  -     ISSN:  1469-5111     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815893     Medline TA:  Int J Neuropsychopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-12     Citation Subset:  -    
Affiliation:
Department of Pharmacology, Faculty for Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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