Agmatine reverses memory deficits induced by Aβ1-42 peptide in mice: A key role of imidazoline receptors

Agmatine is a biogenic amine synthesized following decarboxylation of L-arginine by the enzyme arginine decarboxylase and exhibits favourable outcome in neurodegenerative disorders. Present study was designed to examine the relationship between agmatine and the imidazoline receptors in memory deficits induced by v peptide in mice. Mice were treated with single intracerebroventricular (i.c.v.) injection of A beta(1-42) peptide (3 mu g) and evaluated for learning and memory in Morris water maze (MWM) and subjected to A beta(1-42), TNF-alpha and IL-6 and BDNF immunocontent analysis within the hippocampus. While the learning and memory impairment was evident in the mice subjected to MWM test following A beta(1-42) peptide administration, there was a significant increase in A beta(1-42), TNF-alpha and IL-6 and reduction in BDNF immunocontent within the hippocampus. Daily intraperitoneal (i.p.) treatment with agmatine (10 and 20 mg/kg); imidazoline I-1 receptor agonist, moxonidine and imidazoline I-2 receptor agonist, 2-BFI starting from day 8 to 27 post-A beta(1-42) injection, significantly prevented the cognitive deficits and normalized the A beta(1-42) peptide, IL-6, TNF-alpha and BDNF immunocontent in hippocampus. On the other hand, pre-treatment with imidazoline I-1 receptor antagonist, efaroxan and imidazoline 12 receptor antagonist, BU 224 attenuated the effects of agmatine on learning and memory in MWM, IL-6, TNF-alpha and BDNF content. In conclusion, the present study provides functional evidence for the involvement of the imidazoline receptors in agmatine induced reversal of A beta(1-42) induced memory deficits in mice. The data projects agmatine and imidazoline receptor agonists as a potential therapeutic target for the treatment of AD.