60. Nuclear factor interleukin 6 deficient mice show alterations in the stress-axis and the serotonin metabolism

Abstract

The transcription factor nuclear factor interleukin-6 (NF-IL6) has previously been proposed to be involved in stress-responses. Stress is also known to influence the serotonin system, which is important for the development of depressive disorders. Here, we aimed to further investigate the role of NF-IL6 on the stress-axis and the melatonin system using NF-IL6 deficient mice (NF-IL6KO). NF-IL6KO and wildtype mice (WT) were psychologically stressed with a novel environment followed by immunological stress (2.5 mg/kg Lipopolysaccharide, LPS) a few days later. Motor activity was measured by a telemetric system; 8 or 24 h later animals were sacrificed, brains and blood samples collected and analyzed using RT-PCR and ELISA. NF-IL6KO showed dramatically reduced activity under basal or LPS-stimulated conditions but enhanced activity in response to psychological stress compared to WT. These findings were accompanied by reduced proopiomelanocortin expression 8 h after LPS-stimulation and an abolished day-night-rhythm in corticosterone plasma levels in NF-IL6KO. In addition, NF-IL6KO showed reduced expression of the indolamine-2,3-dioxygenase 8 h after LPS-stimulation, while tryptophan hydroxylase 2 was enhanced; both known as major enzymes for serotonin metabolism. Moreover, expression of the serotonin transporter was enhanced basally and after LPS-stimulation. Overall, we strengthened the implication of NF-IL6 in stress-responses and showed, for the first time, that NF-IL6 seems to be involved in serotonin metabolism. Thus, modulation of NF-IL6-activity might have therapeutic potential for stress- or depressive disorders.