Evidences for agmatine alterations in Aβ1-42induced memory impairment in mice

Abstract

Alzheimer's disease is an age related progressive neurodegenerative disorder characterized by decline in cognitive functions, such as memory loss and behavioural abnormalities. The present study sought to assess alterations in agmatine metabolism in the beta-amyloid (Aβ1–42) Alzheimer’s disease mouse model. Aβ1–42 injected mice showed impairment of cognitive functioning as evidenced by increased working and reference memory errors in radial arm maze (RAM). This cognitive impairment was associated with a reduction in the agmatine levels and elevation in its degrading enzyme, agmatinase, whereas reduced immunocontent was observed in its synthesizing enzyme arginine decarboxylase expression within hippocampus and prefrontal cortex. Chronic agmatine treatment and its endogenous modulation by l-arginine, or arcaine or aminoguanidine prevented the learning and memory impairment induced by single intracranial Aβ1–42 peptide injection. In conclusion, the present study suggests the importance of the endogenous agmatinergic system in β-amyloid induced memory impairment in mice.