Use-dependent effects of amyloidogenic fragments of beta-amyloid precursor protein on synaptic plasticity in rat hippocampus in vivo
SCIE
SCOPUS
- Title
- Use-dependent effects of amyloidogenic fragments of beta-amyloid precursor protein on synaptic plasticity in rat hippocampus in vivo
- Authors
- Kim, JH; Anwyl, R; Suh, YH; Djamgoz, MBA; Rowan, MJ
- Date Issued
- 2001-02-15
- Publisher
- SOC NEUROSCIENCE
- Abstract
- The Alzheimer's disease-related beta -amyloid precursor protein (beta -APP) is metabolized to a number of potentially amyloidogenic peptides that are believed to be pathogenic. Application of relatively low concentrations of the soluble forms of these peptides has previously been shown to block high-frequency stimulation-induced long-term potentiation (LTP) of glutamatergic transmission in the hippocampus. The present experiments examined how these peptides affect low-frequency stimulation-induced long-term depression (LTD) and the reversal of LTP (depotentiation). We discovered that beta -amyloid peptide (A beta1-42) and the A beta -containing C-terminus of beta -APP (CT) facilitate the induction of LTD in the CA1 area of the intact rat hippocampus. The LTD was frequency- and NMDA receptor-dependent. Thus, although low-frequency stimulation alone was ineffective, after intracerebroventricular injection of A beta1-42, it induced an LTD that was blocked by D-(-)-2-amino-5-phosphonopentanoic acid. Furthermore, an NMDA receptor-dependent depotentiation was induced in a time-dependent manner, being evoked by injection of CT 10 min, but not 1 hr, after LTP induction. These use- and time-dependent effects of the amyloidogenic peptides on synaptic plasticity promote long-lasting reductions in synaptic strength and oppose activity-dependent strengthening of transmission in the hippocampus. This will result in a profound disruption of information processing dependent on hippocampal synaptic plasticity.
- Keywords
- Alzheimer' s disease; long-term potentiation (LTP); long-term depression (LTD); depotentiation; amyloid beta peptide (A beta); C terminus fragment; beta-amyloid precursor protein (beta-APP); LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; IN-VIVO; TRANSGENIC MICE; DENTATE GYRUS; AREA CA1; 1-5 HZ; DEPRESSION; TRANSMISSION; STIMULATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28380
- ISSN
- 0270-6474
- Article Type
- Article
- Citation
- JOURNAL OF NEUROSCIENCE, vol. 21, no. 4, page. 1327 - 1333, 2001-02-15
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