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STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior
- Source :
- Scientific Reports
- Publication Year :
- 2014
-
Abstract
- Experimental evidence suggests a role for the immune system in the pathophysiology of depression. A specific involvement of the proinflammatory cytokine interleukin 6 (IL6) in both, patients suffering from the disease and pertinent animal models, has been proposed. However, it is not clear how IL6 impinges on neurotransmission and thus contributes to depression. Here we tested the hypothesis that IL6-induced modulation of serotonergic neurotransmission through the STAT3 signaling pathway contributes to the role of IL6 in depression. Addition of IL6 to JAR cells, endogenously expressing SERT, reduced SERT activity and downregulated SERT mRNA and protein levels. Similarly, SERT expression was reduced upon IL6 treatment in the mouse hippocampus. Conversely, hippocampal tissue of IL6-KO mice contained elevated levels of SERT and IL6-KO mice displayed a reduction in depression-like behavior and blunted response to acute antidepressant treatment. STAT3 IL6-dependently associated with the SERT promoter and inhibition of STAT3 blocked the effect of IL6 in-vitro and modulated depression-like behavior in-vivo. These observations demonstrate that IL6 directly controls SERT levels and consequently serotonin reuptake and identify STAT3-dependent regulation of SERT as conceivable neurobiological substrate for the involvement of IL6 in depression.
- Subjects :
- musculoskeletal diseases
Male
STAT3 Transcription Factor
medicine.medical_specialty
Serotonin
Gene Expression
Neurotransmission
Serotonergic
Article
Proinflammatory cytokine
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
immune system diseases
Internal medicine
Medicine
Animals
Humans
skin and connective tissue diseases
Interleukin 6
Serotonin transporter
030304 developmental biology
Mice, Knockout
Serotonin Plasma Membrane Transport Proteins
0303 health sciences
Multidisciplinary
biology
Behavior, Animal
business.industry
Depression
Interleukin-6
Corrigenda
biological factors
Endocrinology
biology.protein
Antidepressant
business
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....3bf8b44ad7b413fbf73c987359e0e2ad