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

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 β1-42 peptide lacking glutamate-22 (Aβ1-42E22Δ), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid β1-42 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 Aβ1-42E22Δ peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Aβ1-42E22Δ peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Aβ1-42 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 Aβ1-42E22Δ peptide-induced impairment of LTP and spatial learning.