Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excitotoxic stress.
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.
Hanstein
R
R
Institute for Physiological Chemistry and Pathobiochemistry, Department of Pathobiochemistry, Medical School, Johannes Gutenberg-University, Duesbergweg 6, 55099 Mainz, Germany.
Lu
A
A
Wurst
W
W
Holsboer
F
F
Deussing
J M
JM
Clement
A B
AB
Behl
C
C
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
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