1. DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning.
- Author
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Nagata T, Tomiyama T, Mori H, Yaguchi T, and Nishizaki T
- Subjects
- Analysis of Variance, Animals, CA1 Region, Hippocampal physiopathology, Electric Stimulation, Electrophysiology, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Injections, Intraventricular, Long-Term Potentiation physiology, Male, Maze Learning physiology, Rats, Rats, Wistar, Spatial Behavior drug effects, Spatial Behavior physiology, Amyloid beta-Peptides administration & dosage, CA1 Region, Hippocampal drug effects, Caprylates pharmacology, Long-Term Potentiation drug effects, Maze Learning drug effects
- Abstract
Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning.
- Published
- 2010
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