科研之友
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摘要
Immunological activation may result in the development of depressive-like symptoms in a large percentage of patients treated with cytokine-based therapies. The mechanisms underlying susceptibility to cytokine-induced depression are currently unknown; however activation of the tryptophan catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is associated with the induction of cytokine-induced depression. Peripheral administration of lipopolysaccharide (LPS) is one of the most commonly used immunological challenges in animal models of cytokine-induced depression. Inbred mouse strains are useful tools in the investigation of the neurobiology of psychiatric illnesses. In this study we hypothesised that two strains which differ in stress susceptibility, namely the BALB/c and C57BL/6J mice, would respond differentially to LPS and swim-stress in cytokine profile, corticosterone concentrations and mRNA expression of genes coding for the tryptophan metabolising enzymes, 1001,1002, Tph1 and Tph2. The stress-sensitive BALB/c strain exhibited increased depressive-like behaviour and enhanced corticosterone concentrations in response to LPS. Furthermore, swim-stress attenuated the LPS-induced corticosterone response in BALB/c mice only. LPS significantly increased plasma interleukin (IL)-1 beta and tumour necrosis factor alpha (TNF alpha) concentrations to a greater extent in BALB/c mice. The LPS-induced increase in IL-1 beta mRNA expression was significantly attenuated by swim-stress in the hippocampus of C57BL/6J but not in BALB/c mice. TNF alpha mRNA expression was significantly increased in BALB/c mice only; this increase was attenuated by swim-stress. Tph1 mRNA expression was upregulated in the brainstem of C57BL/6J mice post-LPS and following the combination of swim-stress and LPS in BALB/c mice. In the hippocampus Tph1 and Tph2 mRNA expression was increased in C57BL/6J but not BALB/c mice in response to LPS challenge and swim-stress. Conversely, 1002 but not 1001 mRNA expression was significantly altered following swim-stress and LPS, particularly in the hippocampus of BALB/c mice. These data indicate altered central mRNA expression of tryptophan metabolising enzymes and immune activation in BALB/c mice compared to the normo-sensitive C57BL/6J strain.
- 出版日期2012-12-6
