Integration of stress and neuroprotective neuropeptides systems: a comparative approach

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All organisms experience stress during their life. Most forms of stress are caused by injury and disease, but in animals with more complex brains, such and birds and mammals, including humans, psychological and social stress can affect normal physiological processes and lead to neurodegenerative disorders, heightened anxiety, and in some cases infertility. The hormones, corticotropin-releasing factor (CRF) and cortisol, are released from the brain during stressful situations to enable the body to prepare for these challenges. However, if the level of stress is particularly high and continues for a prolonged period, then these hormones can damage brain and other tissues. Fortunately, other hormones in the body may inhibit the actions of these stress-inducing factors. We have discovered a new family of hormones in the brain and reproductive system that inhibit some of the actions of CRF and possibly cortisol. Our studies indicate that these new hormones, called 'teneurin C-terminal associated peptides' (TCAP), can protect the damaging actions on brain cells and reduce anxiety in animals. However, the mechanism by which this occurs is not known. The goal of this proposal is, therefore, to establish what regions of the brain and reproductive system that TCAP acts to modulate CRF and cortisol function. We hypothesize that TCAP is transported directly into the nucleus of cells affected by CRF and cortisol to change gene function to reduce the sensitivity of the damaging stressors.