| Author/Editor | Xiao-Ning, Chen; Meng, Qing-Yuan; Bao, Ai-Min; Swaab, Dick Frans; Wang, Guang-Hui; Zhou, Jiang-Ning | |
| Title | The involvement of retinoic acid receptor-alpha in corticotropin-releasing hormone gene expression and affective disorders | |
| Type | članek | |
| Vol. and No. | Letnik 66, št. 9 | |
| Publication year | 2009 | |
| Volume | str. 832-839 | |
| ISSN | 0006-3223 - Biological psychiatry | |
| Language | eng | |
| Abstract | Background Corticotropin-releasing hormone (CRH) is considered the central driving force in the stress response and plays a key role in the pathogenesis of depression. Retinoic acid (RA) has been suggested by clinical studies to be associated with affective disorders. Methods First, hypothalamic tissues of 12 patients with affective disorders and 12 matched control subjects were studied by double-label immunofluorescence to analyze the expression of CRH and retinoic acid receptor-[alpha] (RAR-[alpha]). Second, critical genes involved in the RA signaling pathways were analyzed in a rat model of depression. Finally, the regulatory effect of RAR-[alpha] on CRH gene expression was studied in vitro. Results We found that the expression of RAR-[alpha] was colocalized with CRH neurons in human hypothalamic paraventricular nucleus (PVN). The density of RAR-[alpha]-immunoreactive neurons and CRH-RAR-[alpha] double-staining neurons was significantly increased in the PVN of patients with affective disorders. The ratio of the CRH-RAR-[alpha] double-staining neurons to the CRH-immunoreactive neurons in affective disorder patients was also increased. Recruitment of RAR-[alpha] by the CRH promoter was observed in the rat hypothalamus. A dysregulated RA metabolism and signaling was also found in the hypothalamus of a rat model for depression. Finally, in vitro studies demonstrated that RAR-[alpha] mediated an upregulation of CRH gene expression. Conclusions These results suggest that RAR-[alpha] might contribute to regulating the activity of CRH neurons in vivo, and the vulnerable character of the critical proteins in RA signaling pathways might provide novel targets for therapeutic strategies for depression. | |
| Keywords | kortikotropin-sproščujoči hormon (CRH) receptor-alfa retinoične kisline afektivne motnje corticotropin-releasing hormone (CRH) retinoic acid receptor-alpha affective disorders |