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

Abstract

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 β-amyloid (Aββ1-42) peptide-induced depression using forced swim test (FST) in mice. Following the 28th days of its administration, Aβ1-42 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-α compared to the control animals. The Aβ1-42 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 Aβ1-42 peptide in mice was potentiated by imidazoline receptor I1 agonist, moxonidine and imidazoline receptor I2 agonist 2-BFI at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan and imidazoline receptor I2 antagonist, idazoxan Also, agmatine levels were significantly reduced in brain samples of β-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 β-amyloid induced a depressive-like behavior in mice. The data projects agmatine as a potential therapeutic target for the AD-associated depression and comorbidities.

• Authors: Nandkishor Kotagale, Rupali Deshmukh, Madhura Dixit, Rajshree Fating, Milind Umekar, Brijesh Taksande
• Journal: Brain research bulletin (Brain Res Bull) Vol. 160 Pg. 56-64 (07 2020) ISSN: 1873-2747 [Electronic] United States
• PMID: 32344125 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Inflammation Mediators
• Peptide Fragments
• amyloid beta-protein (1-42)
• Agmatine

Topics

• Agmatine (pharmacology, therapeutic use)
• Alzheimer Disease (chemically induced, drug therapy, metabolism, psychology)
• Amyloid beta-Peptides (toxicity)
• Animals
• Depression (drug therapy, metabolism, psychology)
• Disease Models, Animal
• Hippocampus (drug effects, metabolism)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Male
• Mice
• Peptide Fragments (toxicity)