The use of the hippocampal slice preparation in the study of Alzheimer's disease.
In the present article we show how studying synaptic mechanisms in hippocampal slice preparations provides information that may be useful in, firstly, the understanding of the aetiology of Alzheimer's disease and, secondly, in the development of novel therapies for dementia. We use several examples, drawn from our own work: (i) The identification of the function of AMPA receptors and NMDA receptors in synaptic transmission and synaptic plasticity. (ii) The discovery of mechanisms that can regulate the activation of NMDA receptors. (iii) The use of transgenic models of Alzheimer's disease. (iv) The identification of a mechanism that can account for the cognitive enhancing effects of the NMDA receptor antagonist memantine. (v) The discovery of a role of glycogen synthase kinase-3beta (tau kinase) in synaptic plasticity.
Fitzjohn
Stephen M
SM
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK.
Doherty
Andrew J
AJ
Collingridge
Graham L
GL
D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D009435:Synaptic Transmission
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D008559:Memantine