The New Neurobiology of Depression

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain (neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoed hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

Intracellular signal transduction of interleukin-6 production bylipopolysaccharide-stimulated fibroblasts / 대한내과학회지

OBJECTIVES: Stimulation of cell results in a variety of early biochemical events, known as signal transduction pathway and ultimately leads to final outcome like cell proliferation or cytokine production. The intracellular signal transduction pathway of IL-6 production by LPS stimulated fibroblast is not well defined. In present study, we investigated what signal transduction pathway is involved in IL-6 production. METHODS: We examined the effects of various inhi bitors of signal transduction pathway including pertussis toxin, cholera toxin, genistein, indomethacin, EDTA, nife dpine, sphingosine, staurosporine, and H8 on the produc tion of IL-6 by human fetal fibroblast MRC-5 after stimulation with LPS. IL-6 was measured by bioassay in supernatant of LPS stimulated fibroblast MRC-5 after pretreatment with inhibitors. RESULTS: Calcium inhibitor (EDTA) and protein kinase inhibitor (staurosporine) reduced IL-6 production by LPS stimulated fibroblast. Protein tyrosine kinase inhibitor(Genistein) and PKC inhibitor(sphingosine) had no influence on IL-6 production. Cholera toxin and pro staglandin inhibitor (indomethacin) led to increase in IL-6 production by LPS stimulated fibroblasts. CONCLUSION:: These results suggest that G protein associated receptors, through the calcium dependent pathway, are working in IL-6 production by LPS stim ulated fibroblasts.