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Тезисы докладов

Первое пленарное заседание

Hyperactivity of the HPA axis is the main feature of depressive disorder. Cytokines -diverse group of polypeptides, products of the immune system activate the HPA axis function under stress or inflammatory challenge. Recently there has been increasing interest in the potential role of the immune system in the neuroendocrine and behavior features of depressive and anxiety disorders. Leukemia inhibitory factor (LIF) a is a pleiotropic cytokine with diverse biological activity. We showed earlier that LIF and LIF receptors are expressed in the HPA axis. LIF regulates differentiation and development of murine pituitary corticotrophs early in ontogenesis, potently induces proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC gene expression. The goal of this study was to investigate a possible contribution of LIF as a mediator of the HPA axis to the neurobiology of depression. We demonstrate here that the lack of LIF in LIF knockout (LIFKO) animals resulted in decreased hypothalamic CRH and PACAP responses to inflammatory stress (p<0.05). Highly elevated glucocorticoid receptor (GR) mRNA levels are observed in hippocampus, hypothalamus, pituitary and on the periphery (p<0.05) in LIF knockout mice and these receptors are more functionally active than in WT animals. On the contrary, LIF suppresses GR expression in vivo and in vitro. High levels of GR results in a hypo-activity of the HPA axis in LIFKO mice. Animals with LIF deficiency show anti-depressive behavior: increased mobility in forced swim test (p<0.001) with no changes in locomotor behavior. Chronic treatment with antidepressant imipramine abrogated depressive symptoms and markedly attenuated LPS-induced stimulation of hypothalamic LIF in normal mice. This attenuation was accompanied by decline in the HPA axis activity and significant increase in GR mRNA levels in hippocampus, similar to what was observed in LIF deficient animals. Mice lacking CRH (CRHKO) have increased induction of hypothalamic and pituitary LIF and show depressive-like behavior in a forced swim test. These results suggest that central LIF may be implicated in developing of depressive symptoms.

Примечание. Тезисы докладов публикуются в авторской редакции

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    Дата последней модификации: 06-Jul-2012 (11:45:21)