Protective Effects of Agmatine Against Corticosterone-Induced Impairment on Hippocampal mTOR Signaling and Cell Death
| Autor: | Gislaine Olescowicz, Ana Lúcia S. Rodrigues, Cristine de Paula Nascimento-Castro, Tuane Bazanella Sampaio, Joana Gil-Mohapel, Patricia S. Brocardo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death medicine.medical_specialty Agmatine Anti-Inflammatory Agents Hippocampus Hippocampal formation Toxicology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Corticosterone Internal medicine Fluoxetine medicine Animals PI3K/AKT/mTOR pathway Neurons Cell Death Chemistry General Neuroscience Dentate gyrus TOR Serine-Threonine Kinases 030104 developmental biology Endocrinology Neuroprotective Agents Dentate Gyrus Signal transduction 030217 neurology & neurosurgery Selective Serotonin Reuptake Inhibitors |
| Zdroj: | Neurotoxicity research. 38(2) |
| ISSN: | 1476-3524 |
| Popis: | 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 (Ser2448), a pro-survival protein that is active when phosphorylated at Ser2448, 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. |
| Databáze: | OpenAIRE |
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