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We used murine neocortical cultures derived from transgenic and knock-in mice to test the effect of expression of expanded polyglutamine-containing huntingtin on neuronal vulnerability to excitotoxins or other insults. Neurons cultured from mice expressing either a normal length (Hdh(Q20)) or expanded (Hdh(Q111)) CAG repeat as a knock-in genetic alteration in exon one of the mouse Hdh gene [Hum Mol Genet 8 (1999) 115] had similar vulnerability to N-methyl-D-aspartate (NMDA) and kainate-mediated excitotoxicity. These neurons also exhibited similar vulnerability to oxidative stress (24 h exposure to 10-100 microM paraquat or 1-10 microM menadione), apoptosis (48 h exposure to 30-100 nM staurosporine or 1 microM dizocilpine maleate (MK-801) and proteasome inhibition (48 h exposure to 0.3-3 microM MG-132). Neocortical neurons cultured from mice transgenic for an expanded CAG repeat-containing exon 1 of the human HD gene (Mangiarini et al., 1996, R6/2 line) and non-transgenic littermate controls also had similar vulnerability to NMDA and kainate-mediated excitotoxicity. These observations suggest that expression of expanded polyglutamine-containing huntingtin does not acutely alter the vulnerability of cortical neurons to excitotoxic, oxidative or apoptotic insults."}

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":147},"obj":"DRI_Background"},{"id":"T2","span":{"begin":148,"end":284},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":285,"end":503},"obj":"DRI_Approach"},{"id":"T4","span":{"begin":504,"end":800},"obj":"DRI_Background"},{"id":"T5","span":{"begin":801,"end":920},"obj":"DRI_Background"},{"id":"T6","span":{"begin":921,"end":937},"obj":"Token_Label.OUTSIDE"},{"id":"T7","span":{"begin":937,"end":996},"obj":"DRI_Background"},{"id":"T8","span":{"begin":997,"end":1015},"obj":"Token_Label.OUTSIDE"},{"id":"T9","span":{"begin":1016,"end":1076},"obj":"DRI_Background"},{"id":"T10","span":{"begin":1077,"end":1096},"obj":"Token_Label.OUTSIDE"},{"id":"T11","span":{"begin":1096,"end":1098},"obj":"DRI_Background"},{"id":"T12","span":{"begin":1099,"end":1255},"obj":"DRI_Background"},{"id":"T13","span":{"begin":1256,"end":1281},"obj":"Token_Label.OUTSIDE"},{"id":"T14","span":{"begin":1282,"end":1366},"obj":"DRI_Background"},{"id":"T15","span":{"begin":1367,"end":1566},"obj":"DRI_Outcome"}],"text":"Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: unaltered vulnerability to excitotoxins and other insults.\nGlutamate-mediated excitotoxicity might contribute to the pathogenesis of Huntington's disease and other polyglutamine repeat disorders. We used murine neocortical cultures derived from transgenic and knock-in mice to test the effect of expression of expanded polyglutamine-containing huntingtin on neuronal vulnerability to excitotoxins or other insults. Neurons cultured from mice expressing either a normal length (Hdh(Q20)) or expanded (Hdh(Q111)) CAG repeat as a knock-in genetic alteration in exon one of the mouse Hdh gene [Hum Mol Genet 8 (1999) 115] had similar vulnerability to N-methyl-D-aspartate (NMDA) and kainate-mediated excitotoxicity. These neurons also exhibited similar vulnerability to oxidative stress (24 h exposure to 10-100 microM paraquat or 1-10 microM menadione), apoptosis (48 h exposure to 30-100 nM staurosporine or 1 microM dizocilpine maleate (MK-801) and proteasome inhibition (48 h exposure to 0.3-3 microM MG-132). Neocortical neurons cultured from mice transgenic for an expanded CAG repeat-containing exon 1 of the human HD gene (Mangiarini et al., 1996, R6/2 line) and non-transgenic littermate controls also had similar vulnerability to NMDA and kainate-mediated excitotoxicity. These observations suggest that expression of expanded polyglutamine-containing huntingtin does not acutely alter the vulnerability of cortical neurons to excitotoxic, oxidative or apoptotic insults."}