Huntington's disease transgenic mice are resistant to global cerebral ischemia.
Excitotoxicity plays a key role in ischemic neuronal death and is also one of the candidate mechanisms contributing to neurodegeneration in Huntington's disease (HD). Unexpectedly we have now found that transgenic mice expressing exon 1 of a mutant human HD gene (R6/1) are protected against global cerebral ischemia (GCI), installed by temporary bilateral occlusion of the carotid arteries. Whereas wild type mice showed a substantial neuronal damage in the hippocampus following 15, 20 and 60 min of GCI, transgenic mice were partially protected after 15 and 20 minutes of hypoxemia. This tolerance to ischemia is not blocked by pretreatment of mice with cycloheximide, an unspecific protein synthesis inhibitor. We conclude that this form of tolerance to ischemia in HD transgenic mice--although somewhat reminiscent of ischemic tolerance after ischemic preconditioning--is therefore independent of short term expression of endogenous neuroprotective proteins.
Schiefer
Johannes
J
University Hospital RWTH Aachen, Department of Neurology, Aachen, Germany.
Alberty
Anke
A
Dose
Tatjana
T
Oliva
Sabine
S
Noth
Johannes
J
Kosinski
Christoph M
CM
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D005091:Exons; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D003513:Cycloheximide