Agmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic rats

Agmatine, a polycationic amine synthesized via decarboxylation of l-arginine by arginine decarboxylase is reported to exhibit anti-hyperglycemic, antioxidant and memory enhancing effects. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze and object recognition paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with agmatine (5-10 mg/kg, i.p. for 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. Further, memory improving effects of agmatine were independent of adrenal I(2) imidazoline receptors. In a separate set, agmatine treatment for an initial 15 days after diabetes confirmation also significantly reduced memory impairment during training trials after 30 days of diabetes confirmation. Moreover, treatment during training trials (30 days after diabetes) also significantly reduced memory impairment in diabetic rats. In conclusion, the present study demonstrates that treatment with agmatine prevents changes in oxidative stress and ChE activity, and probably consequent memory impairment in diabetic rats.

► Agmatine protects against cognitive dysfunction induced by streptozotocin in rats. ► These protective effects of agmatine could be multivariate. ► Antidiabetic, antioxidant, and ChE inhibition contributes to the effect of agmatine. ► Imidazoline receptor and corticosteroid activity modulation may be involved in the effect of agmatine.