Agmatine protects against beta-amyloid25-35-induced memory impairments in the rat.
Amyloid beta fragment 25-35 (Abeta(25-35)) is the neurotoxic domain of the full-length Abeta(1-42) and causes memory impairments in rodents. Recent research suggests that agmatine, decarboxylated arginine, has a neuroprotective role. This study investigated the effects of a single bilateral i.c.v. infusion of aggregated Abeta(25-35) (30 nmol) in a battery of behavioural tests conducted during the period 4-6 (Experiment 1) and 4-14 (Experiment 2) weeks post-Abeta(25-35) infusion, and evaluated the protective effect of agmatine (40 mg/kg) administered i.p. 30 min prior to Abeta(25-35) infusion and once daily for a further nine consecutive days. In Experiment 1, Abeta(25-35) rats with saline treatment were not impaired in the elevated plus maze and open field and mildly impaired in the reference memory version of the water maze task, but performed poorly in the working memory version of the water maze task and the object recognition memory task, relative to the control rats that received the i.c.v. infusion of Abeta(35-25) (inactive peptide) and saline treatment. By contrast, Abeta(25-35) rats with agmatine treatment did not show performance impairments in the working memory version of the water maze task and the object recognition memory task. In Experiment 2, Abeta(25-35) rats with saline treatment were significantly impaired in the standard radial arm maze task, but only displayed no or very mild impairments in the delayed non-match to position and reference memory versions of the radial arm maze task, T-maze, object recognition memory task, both the reference and working memory versions of the water maze task, elevated plus maze and open field. By contrast, Abeta(25-35) rats with agmatine treatment were not impaired in the standard radial arm maze and performed even better than the controls in the reference memory version of the task. These results demonstrate that agmatine is able to protect against Abeta(25-35)-induced memory deficits.
Bergin
D H
DH
Department of Anatomy and Structural Biology, School of Medical Sciences, Brain Health and Repair Research Centre, University of Otago, Dunedin, New Zealand.
Liu
P
P
D000376:Agmatine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000376:Agmatine