Functions of the Signal Transducer and Activator of Transcription 6 in a Behavioral Animal Model of Depression.

ABSTRACT

AIMS: Depression is one of the most common inflammatory and mental disorders. Signal transducer and activator of transcription 6 (STAT6) plays a crucial role in the pathology of mental disorders as well as inflammatory diseases. METHODS: Here we determined the role of STAT6 in the pathogenesis of depression using STAT6-deficient mice in a forced swimming test. RESULTS: The immobility time was significantly decreased in STAT6-deficient mice compared to wild-type mice without alteration of locomotor activity. STAT6-deficient mice exhibited a significantly enhancing dopamine and 5-hydroxytryptamine (5-HT, serotonin) in brain. In addition, the expression of serotonin transporter in the hippocampus was markedly downregulated in STAT6-deficient mice. These results provide the first evidence that STAT6 affects depressive-like behavior through downregulating monoamines, including dopamine and 5-HT in the hippocampus of brain. CONCLUSIONS: In conclusion, identification of STAT6 signaling pathways on depression might open new perspectives for antidepressant therapies.