Integration of stress and neuroprotective neuropeptides systems: a comparative approach

所有生物在其一生中都会经历压力。大多数形式的压力是由伤害和疾病引起的，但在具有更复杂大脑的动物中，如鸟类和哺乳动物，包括人类，心理和社会压力会影响正常的生理过程，导致神经退行性疾病、焦虑加剧，在某些情况下还会导致不孕。荷尔蒙，促肾上腺皮质激素释放因子（CRF）和皮质醇，在压力情况下从大脑释放，使身体为这些挑战做好准备。然而，如果压力水平特别高，并持续很长一段时间，那么这些激素就会损害大脑和其他组织。幸运的是，体内的其他激素可能会抑制这些应激诱导因素的作用。我们在大脑和生殖系统中发现了一个新的激素家族，它可以抑制CRF的一些活动，可能还有皮质醇。我们的研究表明，这些被称为“腱神经蛋白c端相关肽”（TCAP）的新激素可以保护对脑细胞的破坏作用，并减少动物的焦虑。然而，发生这种情况的机制尚不清楚。因此，这项建议的目标是确定TCAP作用于大脑和生殖系统的哪些区域来调节CRF和皮质醇功能。我们假设TCAP被直接转运到受CRF和皮质醇影响的细胞核中，从而改变基因功能，降低对破坏性应激源的敏感性。

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.