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Brain

Year: 2010  |  Volume: 133  |  Issue: 10  |  Page No.: 3069 - 3079

Dendritic cell nuclear protein-1, a novel depression-related protein, upregulates corticotropin-releasing hormone expression

T Zhou, S Wang, H Ren, X. R Qi, S Luchetti, W Kamphuis, J. N Zhou, G Wang and D. F. Swaab

Abstract

The recently discovered dendritic cell nuclear protein-1 is the product of a novel candidate gene for major depression. The A allele encodes full-length dendritic cell nuclear protein-1, while the T allele encodes a premature termination of translation at codon number 117 on chromosome 5. In the present study we investigate whether the two forms of dendritic cell nuclear protein-1 might act on corticotropin-releasing hormone, which plays a crucial role in the stress response and in the pathogenesis of depression. The messenger RNA expression of dendritic cell nuclear protein-1 appeared to be increased in the laser micro-dissected paraventricular nucleus of patients with depression compared with control subjects. Dendritic cell nuclear protein-1 was also found to be co-localized with corticotropin-releasing hormone in paraventricular nucleus neurons. Moreover, full-length dendritic cell nucleus protein-1 bound to and transactivated the promoter of corticotropin-releasing hormone in human embryonic kidney 293 cells. We propose that full-length dendritic cell nucleus protein-1 may play a role in the pathogenesis of depressive disorders by enhancing corticotropin-releasing hormone expression in the hypothalamic paraventricular nucleus.

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