Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excitotoxic stress

R. Hanstein, A. Lu, W. Wurst, F. Holsboer, J. M. Deussing, A. B. Clement, C. Behl

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)712-721
Number of pages10
JournalNeuroscience
Volume156
Issue number3
DOIs
StatePublished - Oct 15 2008
Externally publishedYes

Fingerprint

Corticotropin-Releasing Hormone
Kainic Acid
Brain-Derived Neurotrophic Factor
Neuroprotective Agents
Neuronal Plasticity
Epilepsy
Hippocampus
Cell Survival
Learning
Neurons

Keywords

  • BDNF
  • CRH
  • excitotoxicity
  • neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excitotoxic stress. / Hanstein, R.; Lu, A.; Wurst, W.; Holsboer, F.; Deussing, J. M.; Clement, A. B.; Behl, C.

In: Neuroscience, Vol. 156, No. 3, 15.10.2008, p. 712-721.

Research output: Contribution to journalArticle

Hanstein, R. ; Lu, A. ; Wurst, W. ; Holsboer, F. ; Deussing, J. M. ; Clement, A. B. ; Behl, C. / Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excitotoxic stress. In: Neuroscience. 2008 ; Vol. 156, No. 3. pp. 712-721.
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