Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine

Zaman, S. H., Parent, A., Laskey, A., Lee, M. K., Borchelt, D. R., Sisodia, S. S., Malinow, R. (2000) Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine. Neurobiology of Disease, 7 (1). pp. 54-63. ISSN 0969-9961

URL: http://www.ncbi.nlm.nih.gov/pubmed/10671322
DOI: 10.1006/nbdi.1999.0271

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: LONG-TERM POTENTIATION AMYLOID PRECURSOR PROTEIN IN-VIVO ENDOPLASMIC-RETICULUM BETA-PEPTIDE LOCALIZATION MEMORY CELLS BRAIN HIPPOCAMPUS
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
Investigative techniques and equipment > electrophysiology > brain slice
Investigative techniques and equipment > electrophysiology
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic transmission
CSHL Authors:
Communities: CSHL labs > Malinow lab
Depositing User: Matt Covey
Date Deposited: 31 Jan 2014 16:17
Last Modified: 31 Jan 2014 16:17
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29384

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