Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine.
Mutations in presenilin 1 (PS1) are the most common causes of familial Alzheimer's disease (FAD). We examined synaptic physiology in hippocampal brain slices of transgenic mice expressing the FAD-linked PS1 deletion of exon 9 variant. Basal excitatory transmission and paired-pulse facilitation in PS1 mutant mice were unchanged. Short- and long-term potentiation of excitatory transmission following high-frequency stimulation were greater in transgenic mice expressing mutant PS1. Mutants had enhanced synaptic inhibition, which may be a compensatory change offsetting an abnormally sensitized plasticity of excitatory transmission. Increasing inhibitory transmission in mutant animals even more with a benzodiazepine reverted synaptic potentiation to the levels of controls. These results support the potential use of benzodiazepines in the treatment of familial Alzheimer's disease.
Zaman
S H
SH
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724-0100, USA.
Parent
A
A
Laskey
A
A
Lee
M K
MK
Borchelt
D R
DR
Sisodia
S S
SS
Malinow
R
R
D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005091:Exons; D005445:Flunitrazepam / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D014644:Genetic Variation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1; D017384:Sequence Deletion; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D014151:Anti-Anxiety Agents; D058787:GABA-A Receptor Antagonists; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D005445:Flunitrazepam