title: Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity.
abstract: Excitotoxic brain lesions, such as stroke and epilepsy, lead to increasing destruction of neurons hours after the insult. The deadly cascade of events involves detrimental actions by free radicals and the activation of proapoptotic transcription factors, which finally result in neuronal destruction. Here, we provide direct evidence that the nutritionally essential trace element selenium has a pivotal role in neuronal susceptibility to excitotoxic lesions. First, we observed in neuronal cell cultures that addition of selenium in the form of selenite within the physiological range protects against excitotoxic insults and even attenuates primary damage. The neuroprotective effect of selenium is not directly mediated via antioxidative effects of selenite but requires de novo protein synthesis. Gel shift analysis demonstrates that this effect is connected to the inhibition of glutamate-induced NF-kappaB and AP-1 activation. Furthermore, we provide evidence that selenium deficiency in vivo results in a massive increase in susceptibility to kainate-induced seizures and cell loss. These findings indicate the importance of selenium for prevention and therapy of excitotoxic brain damage.
authors.affiliation: Institute of Anatomy, Department of Cell and Neurobiology, Humboldt University Medical School Charité, D-10115 Berlin, Germany. nicolai.savaskan@charite.de
authors.forename: Nicolai E
authors.initials: NE
authors.lastname: Savaskan
authors.forename: Anja U
authors.initials: AU
authors.lastname: Bräuer
authors.forename: Markus
authors.initials: M
authors.lastname: Kühbacher
authors.forename: Ilker Y
authors.initials: IY
authors.lastname: Eyüpoglu
authors.forename: Antonios
authors.initials: A
authors.lastname: Kyriakopoulos
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.forename: Dietrich
authors.initials: D
authors.lastname: Behne
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D004198:Disease Susceptibility; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000473:pathology; D008959:Models, Neurological; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D012643:Selenium / Q000172:deficiency* / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016328:NF-kappa B; D018696:Neuroprotective Agents; D018808:Transcription Factor AP-1; D018698:Glutamic Acid; D012643:Selenium