Agmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic rats.
Progress in neuro-psychopharmacology & biological psychiatry 2012 Jan 25; In press
Bhutada P, Mundhada Y, Humane V, Rahigude A, Deshmukh P, Latad S, Jain K
Sinhgad College of Pharmacy, Post-Graduate Research Department, Off Sinhgad road, Vadgaon (Bk), Pune 41, Maharashtra, India.
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 (5-10mg/kg, i.p. for 30days) 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 15days after diabetes confirmation also significantly reduced memory impairment during training trials after 30days of diabetes confirmation. Moreover, treatment during training trials (30days 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.