PubMed:10471078 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10471078","sourcedb":"PubMed","sourceid":"10471078","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10471078","text":"Memantine restores long term potentiation impaired by tonic N-methyl-D-aspartate (NMDA) receptor activation following reduction of Mg2+ in hippocampal slices.\nThis study compared the ability of memantine and (+)MK-801 to counteract deficits in the induction of long term potentiation (LTP) following reduction of Mg2+ in hippocampal slices--a model of increased synaptic noise due to tonic N-methyl-D-aspartate (NMDA) receptor activation. Decreasing Mg2+ from 1 mM to 10 microM for 60 min enhanced baseline field excitatory post-synaptic potential (fEPSP) slopes (87.2 +/- 10.6% above control) and impaired LTP (-4.1 +/- 9.8% compared to pre-tetanic levels). Long pre-incubations with memantine (1 microM), a concentration achieved in the CSF of dementia patients, almost fully restored the induction of LTP (to 43.4 +/- 8.4%) without changing the enhancement of baseline fEPSP slopes (84.1 +/- 11.6%). Memantine (10 microM) fully restored the induction of LTP (61.5 +/- 5.3%) and also decreased the enhancement of baseline fEPSP slopes (30.1 +/- 4.9%). In contrast, although (+)MK-801 (0.01, 0.1 and 1 microM) caused a concentration-dependent reduction in the low Mg2+ -induced enhancement of baseline fEPSP slopes, it was not able to restore the induction of LTP (3.0 +/- 9.8%, 16.3 +/- 5.7% and 4.8 +/- 6.7% respectively). These data indicate that memantine could produce symptomatological improvement in learning under conditions of tonic NMDA receptor activation such as those occurring in chronic neurodegenerative diseases whereas (+)MK-801 is likely to have only negative effects.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":746,"end":754},"obj":"HP_0000726"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"}]},{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":158},"obj":"DRI_Background"},{"id":"T2","span":{"begin":159,"end":438},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":439,"end":658},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":659,"end":902},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":903,"end":1053},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":1054,"end":1164},"obj":"DRI_Outcome"},{"id":"T7","span":{"begin":1165,"end":1178},"obj":"Token_Label.OUTSIDE"},{"id":"T8","span":{"begin":1179,"end":1325},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":1326,"end":1588},"obj":"DRI_Challenge"}],"attributes":[{"subj":"T1","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T2","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T3","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T4","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T5","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T6","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T7","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T8","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T9","pred":"source","obj":"UseCases_ArguminSci_Discourse"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#c293ec","default":true},{"id":"UseCases_ArguminSci_Discourse","color":"#93eca8"}]}]}}