Agmatine protects against β-amyloid25-35-induced memory impairments in the rat

Amyloid beta fragment 25-35 (Aβ25-35) is the neurotoxic domain of the full-length Aβ1-42 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 Aβ25-35 (30 nmol) in a battery of behavioural tests conducted during the period 4–6 (Experiment 1) and 4–14 (Experiment 2) weeks post-Aβ25-35 infusion, and evaluated the protective effect of agmatine (40 mg/kg) administered i.p. 30 min prior to Aβ25-35 infusion and once daily for a further nine consecutive days. In Experiment 1, Aβ25-35 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 Aβ35-25 (inactive peptide) and saline treatment. By contrast, Aβ25-35 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, Aβ25-35 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, Aβ25-35 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 Aβ25-35-induced memory deficits.