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TRANSGENIC OVEREXPRESSION OF CORTICOTROPIN RELEASING HORMONE PROVIDES PARTIAL PROTECTION AGAINST NEURODEGENERATION IN AN IN VIVO MODEL OF ACUTE EXCITOTOXIC STRESS

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons80425

Lu,  A.
AG Almeida, Osborne, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80599

Wurst,  W.
Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80372

Holsboer,  F.
Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80301

Deussing,  J. M.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80263

Behl,  C.
Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Hanstein, R., Lu, A., Wurst, W., Holsboer, F., Deussing, J. M., Clement, A. B., et al. (2008). TRANSGENIC OVEREXPRESSION OF CORTICOTROPIN RELEASING HORMONE PROVIDES PARTIAL PROTECTION AGAINST NEURODEGENERATION IN AN IN VIVO MODEL OF ACUTE EXCITOTOXIC STRESS. Neuroscience, 156(3), 712-721.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-93AD-B
Abstract
Corticotropin releasing hormone (CRH) is the central modulator of the mammalian hypothalamic-pituitaryadrenal (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 over-expressing 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 neuro-inflammation 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. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.