Peer-Reviewed Journal Details
Mandatory Fields
Malynn, S;Campos-Torres, A;Moynagh, P;Haase, J
2013
April
Neurochemical Research
The Pro-inflammatory Cytokine TNF-alpha Regulates the Activity and Expression of the Serotonin Transporter (SERT) in Astrocytes
Published
59 ()
Optional Fields
NECROSIS-FACTOR-ALPHA MESSENGER-RNA GENE-EXPRESSION RAT-BRAIN PHARMACOLOGICAL CHARACTERIZATION CHORIOCARCINOMA CELLS MAJOR DEPRESSION INTERFERON-ALPHA UP-REGULATION 5-HTT GENE
38
694
704
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 factor-alpha (TNF-alpha) 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-alpha resulted in a dose- and time-dependent 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-alpha enhanced the transport capacity (V-max) 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-alpha activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Pre-treatment with the p38 MAPK inhibitor SB203580 attenuated the TNF-alpha 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-alpha, an effect that is at least in part dependent on p38 MAPK activation.
NEW YORK
0364-3190
10.1007/s11064-012-0967-y
Grant Details