Malynn, Sandra and Campos-Torres, Antonio and Moynagh, Paul N. and Haas, Jana (2013) The Pro-inflammatory Cytokine TNF-a Regulates the Activity and Expression of the Serotonin Transporter (SERT) in Astrocytes. Neurochemical Research, 38 (4). pp. 694-704. ISSN 0364-3190

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Abstract

Pro-inflammatory cytokines have been implicated in the precipitation of depression and related disorders, and the antidepressant sensitive serotonin transporter (SERT) may be a major target for immune regulation in these disorders. Here, we focus on astrocytes, a major class of immune competent cells in the brain, to examine the effects of pro-longed treatment with tumor necrosis factoralpha (TNF-a) on SERT activity. We first established that high-affinity serotonin uptake into C6 glioma cells occurs through a SERT-dependent mechanism. Functional SERT expression is also confirmed for primary astrocytes. In both cell types, exposure to TNF-a resulted in a dose- and timedependent increase in SERT-mediated 5-HT uptake, which was sustained for at least 48 h post-stimulation. Further analysis in primary astrocytes revealed that TNF-a enhanced the transport capacity (Vmax) of SERT-specific 5-HT uptake, suggesting enhanced transporter expression, consistent with our observation of an increase in SERT mRNA levels. We confirmed that in both, primary astrocytes and C6 glioma cells, treatment with TNF-a activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Pre-treatment with the p38 MAPK inhibitor SB203580 attenuated the TNF-a mediated stimulation of 5-HT transport in both, C6 glioma and primary astrocytes. In summary, we show that SERT gene expression and activity in astrocytes is subject to regulation by TNF-a, an effect that is at least in part dependent on p38 MAPK activation

Item Type:	Article
Keywords:	5-HT; Serotonin transporter; TNF-a; Pro-inflammatory; cytokines; Astrocytes; Depression;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Institute of Immunology
Item ID:	4979
Identification Number:	https://doi.org/10.1007/s11064-012-0967-y
Depositing User:	Professor Paul Moynagh
Date Deposited:	22 May 2014 10:38
Journal or Publication Title:	Neurochemical Research
Publisher:	Springer Verlag (Germany)
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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