Interaction of BDNF and Connexin43– two downstream targets of CRH-activated gene transcription

Corticotropin-releasing hormone (CRH) is a major central stress mediator, but also a potent neuroprotective effector. In an attempt to unravel the mechanisms by which CRH mediates its neuroprotective actions we identified two downstream targets of CRH-activated gene transcription, the brain-derived neurotrophic factor (BDNF; Bayatti et al., Endocrinology 2005; 146: 1205–1213 and Hanstein et al., Neuroscience 2008; 156 (3):712–21) and the gap junction molecule connexin 43 (Cx43; Hanstein et al., Molecular Endocrinology 2009; in press). Both molecules are known to exert neuroprotective effects and may thus mediate the neuroprotective actions of CRH. By treating neural cells with BDNF and knocking down BDNF expression using BDNF siRNA we could show that BDNF itself upregulates Cx43 expression and enhances gap junction communication. On the contrary, downregulation of Cx43 expression levels by Cx43 siRNA showed no influence on BDNF expression. In summary, our experiments show that CRH may increase gap junction communication by either acting directly on Cx43 gene expression or via an indirect way by stimulation of BDNF expression. Both ways may be involved in the CRH-induced neuroprotection.