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• W1999206875 abstract "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." @default.
• W1999206875 created "2016-06-24" @default.
• W1999206875 creator A5041342670 @default.
• W1999206875 creator A5078688503 @default.
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• W1999206875 date "2011-01-12" @default.
• W1999206875 modified "2023-10-17" @default.
• W1999206875 title "Antidepressants elevate GDNF expression and release from C6 glioma cells in a β-arrestin1-dependent, CREB interactive pathway" @default.
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• W1999206875 doi "https://doi.org/10.1017/s1461145710001550" @default.
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