| Depression is related to the normal emotions of sadness and bereavement, but it does not remit when the external cause of these emotions dissipates, and it is disproportionate to their cause. Classic severe states of depression often have no external precipitating cause. The diagnosis of major depressive disorder requires a distinct change of mood, characterized by sadness or irritability and accompanied by at least several psychophysiological changes, such as disturbances in sleep, appetite, or sexual desire; constipation; loss of the ability to experience pleasure in work or with friends; crying; suicidal thoughts; and slowing of speech and action. These changes must last a minimum of two weeks and interfere considerably with work and family relations. Depression is a heterogeneous disorder with a highly variable course, an inconsistent response to treatment, and no established mechanism. The possible mechanisms of depression include genetics, the monoamine-deficiency hypothesis, the hypothalamic-pituitary-adrenal axis, growth factors and other possible mechanisms. The hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in depression, due to genetic factors or aversive stimuli that may occur during early development or adult life. At least five interacting hypothalamic peptidergic systems are involved in the symptoms of major depression.Corticotropin releasing hormone (CRH) is the key hypothalamic peptide controlling the HPA-axis. It plays a central role in the response of the organism to stress. As a 41-residue hypothalamic peptide, CRH was first described by Vale (Vale et al.1981). It could stimulate secretion of corticotropin and beta-endorphin (Vale et al.,1981). CRH is charactered with relative conservation. It was found in human (Shibahara, Morimoto et al.,1983), rat (Rivier, Spiess et al.1983), sheep (Vale, Spiess et al.1981), horse (Livesey, Carne et al.1991) and cow (Esch, Ling et al.1984). There is the same structure feature between human, rat and horse. After exposure to stress, the synthesis of CRH is increased in peptidergic neurons in the paraventricular nucleus (PVN) of the hypothalamus, leading to the release of the peptide from the median eminence. CRH is transported through the portal vascular system to the pituitary, and stimulates the secretion of adrenocorticotropin (ACTH) from anterior pituitary cells (Vale et al.,1981). ACTH is secreted into the systemic circulation, leading (in humans) to the secretion of cortisol from the adrenal cortex. At the last, the cortisol also negative feedback regulated ACTH and CRH again (Erkut, Pool et al. 1998).The recently discovered dendritic cell nuclear protein-1 (DCNPl) is the product of a novel candidate gene for major depression. The A allele encodes full-length DCNP1, while the T allele encodes a premature termination of translation at codon number 117 on chromosome 5 (Willis-Owen, Shifman et al.2006). In the present study we investigate whether the two forms of DCNP1 might act on CRH, which plays a crucial role in the stress response and in the pathogenesis of depression. The mRNA expression of DCNP1 appeared to be increased in the laser micro-dissected PVN of depressed patients as compared to control subjects. In addition, DCNP1 was found to be co-localized with CRH in PVN neurons performed with immunofluorescence and confocal laser scanning microscopy. Moreover, with chromatin immunoprecipitation, immunoblot analysis and dual-luciferase reporter gene assay, full-length DCNP1 bound to and transactivated the promoter of CRH in human embryonic kidney 293 cells. We propose that full-length DCNP1 may play a role in the pathogenesis of depressive disorders by enhancing CRH expression in the hypothalamic paraventricular nucleus.
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