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The newly synthesized linoleic acid derivative DCP‐LA ameliorates memory deficits in animal models treated with amyloid‐β peptide and scopolamine
Author(s) -
NAGATA Tetsu,
YAMAMOTO Satoshi,
YAGUCHI Takahiro,
ISO Hiroyuki,
TANAKA Akito,
NISHIZAKI Tomoyuki
Publication year - 2005
Publication title -
psychogeriatrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 32
eISSN - 1479-8301
pISSN - 1346-3500
DOI - 10.1111/j.1479-8301.2005.00106.x
Subject(s) - intraperitoneal injection , chemistry , acetylcholinesterase inhibitor , pharmacology , acetylcholinesterase , saline , acetylcholine , donepezil , cholinergic , endocrinology , medicine , biochemistry , dementia , disease , enzyme
Background: In our earlier study, 8‐[2‐(2‐pentyl‐cyclopropylmethyl)‐cyclopropyl]‐octanoic acid (DCP‐LA), a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis ‐double bonds, facilitated hippocampal synaptic transmission by stimulating glutamate release from presynaptic terminals as mediated via α7 acetylcholine (Ach) receptors under the influence of protein kinase C. The present study assessed the possibility of using DCP‐LA as a cognitive enhancer in animal models. Methods: Amyloid‐β 1−40 peptide (300 pM/day) or saline was continuously injected in the right lateral ventricle of rats for 2 weeks. Then, the water maze test was carried out, once per day for 7 days, 1 h after the intraperitoneal injection with DCP‐LA or saline. In a different set of experiments, rats were intraperitoneally injected with scopolamine (1 mg/kg) and the water maze test was performed twice per day, with the first test taking place 1 h after the intraperitoneal injection with DCP‐LA, galantamine or saline, and the second test starting 2 min after the end of the first. Results: Continuous intraventricular injection with amyloid‐β 1−40 peptide in the rat lateral ventricle prolonged the latency for acquisition in the water maze test. DCP‐LA (1 mg/kg, intraperitoneal (i.p.)) significantly improved the impairment, which reached a level similar to the latency for sham. Furthermore, DCP‐LA (1 mg/kg, i.p.) significantly ameliorated learning and memory deficits in rats treated with scopolamine and was, if not more, effective than galantamine, a modest inhibitor of acetylcholinesterase with nicotinic ACh receptor modulation. Conclusion: The results of the present study show that DCP‐LA ameliorates learning and memory deficits induced by amyloid‐β 1−40 peptide or scopolamine. DCP‐LA may thus offer new hope for dementia patients.