title: Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excitotoxic stress.
abstract: 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.
authors: Institute for Physiological Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Medical School, Johannes Gutenberg-University, Duesbergweg 6, 55099 Mainz, Germany.
authors: R
authors: R
authors: Hanstein
authors: A
authors: A
authors: Lu
authors: W
authors: W
authors: Wurst
authors: F
authors: F
authors: Holsboer
authors: J M
authors: JM
authors: Deussing
authors: A B
authors: AB
authors: Clement
authors: C
authors: C
authors: Behl
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000209:etiology* / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins; D020258:Neurotoxicity Syndromes / Q000150:complications* / Q000209:etiology / Q000473:pathology; D037121:Plant Lectins / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D011930:Reaction Time / Q000502:physiology; D012640:Seizures / Q000139:chemically induced
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D007211:Indoles; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016900:Neurofilament Proteins; D037121:Plant Lectins; D011506:Proteins; D022661:RNA, Untranslated; C034981:tomato lectin; C007293:DAPI; D003346:Corticotropin-Releasing Hormone; D007608:Kainic Acid