Corticotropin Releasing Hormone (CRH) targets various neuroprotective mechanisms

Abstract

The corticotropin releasing hormone (CRH) is a central mediator of the human stress response in the central nervous system by affecting the hypothalamic-pituitary adrenal axis. A chronic hyperdrive of the CRH system leads to anxiety-related disorders including depression. Therefore, a stable CRH level is necessary for an appropriate stress response. Furthermore, CRH also affects other central processes, such as learning and memory, synaptic plasticity and mediates neuroprotection. Indeed, CRH induces neuroprotective signalling in a brain region-specific manner by binding to its high-affinity cell surface receptor, the CRH receptor type 1, (Bayatti et al., 2003). Recent studies show that CRH exhibits neuroprotective properties in organotypic hippocampal slices, primary cultures and cell lines in response to certain toxins. Moreover, CRH can directly increase the expression of a potent neuroprotective factor, the brain-derived neurotrophic factor (BDNF) (Bayatti et al., 2005; Elliott-Hunt et al., 2002). Alternatively, neuroprotective effects of CRH may involve the direct modulation of pathways leading to cell death. We investigated activity of CRH in hippocampal slices and observed CRH receptor-mediated neuroprotective action, which may involve MAP kinase activation and BDNF upregulation. Interestingly, CRH unfolds a complex pattern of neuroprotective activities, new targets of CRH activity have been found and are currently under intensive investigation.