Agmatine ameliorates manifestation of depression-like behavior and hippocampal neuroinflammation in mouse model of Alzheimer's disease

摘要

Extensive clinical and experimental studies established that depression and mood disorders are highly prevalent neuropsychiatric conditions in Alzheimer's disease (AD). However, its neurochemical basis is not clearly understood. Thus, understanding the neural mechanisms involved in mediating the co-morbidity of depression and AD may be crucial in exploring new pharmacological treatments for this condition. The present study investigated the role of the agmatinergic system in beta-amyloid (A beta(beta 1-42)) peptide-induced depression using forced swim test (FST) in mice. Following the 28th days of its administration, A beta(1-42) peptide produced depression-like behavior in mice as evidenced by increased immobility time in FST and increased expression of pro-inflammatory cytokines like IL-6 and TNF-alpha compared to the control animals. The A beta(1-42) peptide-induced depression and neuroinflammatory markers were significantly inhibited by agmatine -, moxonidine, 2-BFI and L-arginine by once-daily administration during day 8-27 of the protocol. The antidepressant-like effect of agmatine in A beta(1-42) peptide in mice was potentiated by imidazoline receptor I-1 agonist, moxonidine and imidazoline receptor I-2 agonist 2-BFI at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I-1 antagonist, efaroxan and imidazoline receptor I-2 antagonist, idazoxan Also, agmatine levels were significantly reduced in brain samples of beta-amyloid injected mice as compared to the control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in beta-amyloid induced a depressive-like behavior in mice. The data projects agmatine as a potential therapeutic target for the AD-associated depression and comorbidities.