DCP-LA neutralizes mutant amyloid β peptide-induced impairment of long-term potentiation and spatial learning

• Published in: Behavioural brain research 2010-01, Vol.206 (1), p.151-154
• Main Authors: Nagata, Tetsu, Tominaga, Takemi, Mori, Hiroshi, Yaguchi, Takahiro, Nishizaki, Tomoyuki
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - administration & dosage; Analysis of Variance; Animals; Behavioral psychophysiology; Biological and medical sciences; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - physiopathology; Caprylates - pharmacology; DCP-LA; Electric Stimulation; Electrophysiology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Fundamental and applied biological sciences. Psychology; Injections, Intraventricular; Long-term potentiation; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Mutant amyloid β 1–42; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Wistar; Spatial Behavior - drug effects; Spatial Behavior - physiology; Spatial learning
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2009.08.032

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 β 1–42 peptide lacking glutamate-22 (Aβ 1–42E22Δ), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid β 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 Aβ 1–42E22Δ peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Aβ 1–42E22Δ peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Aβ 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 Aβ 1–42E22Δ peptide-induced impairment of LTP and spatial learning.