Protective Effects of Agmatine Against Corticosterone-Induced Impairment on Hippocampal mTOR Signaling and Cell Death

• Published in: Neurotoxicity research 2020-08, Vol.38 (2), p.319-329
• Main Authors: Olescowicz, Gislaine, Sampaio, Tuane B., de Paula Nascimento-Castro, Cristine, Brocardo, Patricia S., Gil-Mohapel, Joana, Rodrigues, Ana Lúcia S.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Neurobiology; Neurochemistry; Neurology; Neurosciences; Original Article; Pharmacology/Toxicology
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-020-00212-1

Chronic treatment with agmatine, similarly to fluoxetine, may cause antidepressant-like effects mediated, at least in part, by the modulation of hippocampal plasticity. However, the ability of chronic treatment with agmatine to cause antidepressant-like effects associated with the modulation of mammalian target of rapamycin (mTOR) signaling pathway and protection against neuronal death remains to be established. In this study, we investigated the effects of agmatine (0.1 mg/kg, p.o.) and the conventional antidepressant fluoxetine (10 mg/kg, p.o.) treatment on the levels of phosphorylated mTOR (p-mTOR), neuronal death, and overall volume in the hippocampal dentate gyrus (DG) of mice exposed to chronic corticosterone (20 mg/kg, p.o.) treatment for 21 days, a model of stress and depressive-like behavior. Chronic corticosterone treatment increased cell death in the sub-granular zone (SGZ) of the DG, as assessed by Fluoro-Jade B labeling. Agmatine, similarly to fluoxetine, was capable of reversing this alteration in the entire DG, an effect more evident in the ventral portion of the hippocampus. Additionally, reduced phosphorylation of mTOR (Ser 2448 ), a pro-survival protein that is active when phosphorylated at Ser 2448 , was observed in the whole hippocampal DG in corticosterone-treated mice, an effect not observed in agmatine or fluoxetine-treated mice. Chronic exposure to corticosterone caused a significant reduction in overall hippocampal volume, although no alterations were observed between the groups with regards to DG volume. Altogether, the results indicate that agmatine, similar to fluoxetine, was able to counteract corticosterone-induced impairment on mTOR signaling and cell death in hippocampal DG.