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Titolo:
Memantine restores long term potentiation impaired by tonic N-methyl-D-aspartate (NMDA) receptor activation following reduction of Mg2+ in hippocampal slices
Autore:
Frankiewicz, T; Parsons, CG;
Indirizzi:
Merz & Co, Dept Pharmacol, D-60318 Frankfurt, Germany Merz & Co Frankfurt Germany D-60318 harmacol, D-60318 Frankfurt, Germany
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 9, volume: 38, anno: 1999,
pagine: 1253 - 1259
SICI:
0028-3908(199909)38:9<1253:MRLTPI>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
VOLTAGE-DEPENDENCY; CHANNEL BLOCK; ANTAGONISTS; GLUTAMATE; ACID; LTP; KINETICS; NEURONS; MEMORY; MK-801;
Keywords:
long term potentiation; hippocampal slice; N-methyl-D-aspartate receptor; tonic activity; memantine; (+)MK-801; Mg2+;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Parsons, CG Merz & Co, Dept Pharmacol, Eckenheimer Landstr 100-104, D-60318 Frankfurt,Germany Merz & Co Eckenheimer Landstr 100-104 Frankfurt Germany D-60318
Citazione:
T. Frankiewicz e C.G. Parsons, "Memantine restores long term potentiation impaired by tonic N-methyl-D-aspartate (NMDA) receptor activation following reduction of Mg2+ in hippocampal slices", NEUROPHARM, 38(9), 1999, pp. 1253-1259

Abstract

This 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+ from1 mM to 10 mu M 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 mu M), 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 mu M) 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 mu M) 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. (C) 1999 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 04:41:26