Hanstein R, Lu A, Wurst W, Holsboer F, Deussing J M, Clement A B, Behl C
Institute for Physiological Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Medical School, Johannes Gutenberg-University, Duesbergweg 6, 55099 Mainz, Germany.
Neuroscience. 2008 Oct 15;156(3):712-21. doi: 10.1016/j.neuroscience.2008.07.034. Epub 2008 Jul 25.
Corticotropin releasing hormone (CRH) is the central modulator of the mammalian hypothalamic-pituitary-adrenal (HPA) axis. In addition, CRH affects other processes in the brain including learning, memory, and synaptic plasticity. Moreover, CRH has been shown to play a role in nerve cell survival under apoptotic conditions and to serve as an endogenous neuroprotectant in vitro. Employing mice overexpressing murine CRH in the CNS, we observed a differential response of CRH-overexpressing mice (CRH-COEhom-Nes) to acute excitotoxic stress induced by kainate compared with controls (CRH-COEcon-Nes). Interestingly, CRH-overexpression reduced the duration of epileptic seizures and prevented kainate-induced neurodegeneration and neuroinflammation in the hippocampus. Our findings highlight a neuroprotective action of CRH in vivo. This neuroprotective effect was accompanied by increased levels of brain-derived neurotrophic factor (BDNF) in CRH-COEhom-Nes mice, suggesting a potential role for BDNF in mediating CRH-induced neuroprotective actions against acute excitotoxicity in vivo.
促肾上腺皮质激素释放激素（CRH）是哺乳动物下丘脑-垂体-肾上腺（HPA）轴的中枢调节因子。此外，CRH还影响大脑中的其他过程，包括学习、记忆和突触可塑性。此外，CRH已被证明在凋亡条件下对神经细胞存活起作用，并在体外作为内源性神经保护剂。利用在中枢神经系统中过表达小鼠CRH的小鼠，我们观察到与对照组（CRH-COEcon-Nes）相比，过表达CRH的小鼠（CRH-COEhom-Nes）对由海藻酸诱导的急性兴奋性毒性应激有不同的反应。有趣的是，CRH的过表达缩短了癫痫发作的持续时间，并预防了海藻酸诱导的海马神经变性和神经炎症。我们的研究结果突出了CRH在体内的神经保护作用。这种神经保护作用伴随着CRH-COEhom-Nes小鼠中脑源性神经营养因子（BDNF）水平的升高，表明BDNF在介导CRH诱导的体内抗急性兴奋性毒性神经保护作用中可能发挥作用。
