Agmatine potentiates neuroprotective effects of subthreshold concentrations of ketamine via mTOR/S6 kinase signaling pathway

Neurochemistry International
Mauren K TavaresAndiara E Freitas

Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most robust neurobiological findings in the pathophysiology of major depressive disorder (MDD) over the last 40 years. The persistent increase in glucocorticoids levels induces morphological and anatomical changes in the brain, especially in the hippocampus. Ketamine represents a major advance for the treatment of MDD, however the psychotomimetic effects of this compound limit its widespread use. Agmatine is a neuromodulator that has been shown to be a putative novel and well-tolerated antidepressant/augmenter drug. In this study, the exposure of HT22 hippocampal neuronal cell line to corticosterone (50 μM) induced a significant neuronal cell death. Interestingly, the incubation of HT22 cells with the fast-acting antidepressant drug ketamine (1 μM) prevented the corticosterone-induced toxicity. Similarly, agmatine caused a significant cytoprotection at the concentration of 0.1 μM against corticosterone (50 μM) cell damage. Notably, the incubation with a subthreshold concentration of ketamine (0.01 μM) in combination with a subthreshold concentration of agmatine (0.001 μM) prevented the neuronal damage elicited by corticosterone (50 μM). A 24 h co-incub...Continue Reading

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Citations

Feb 16, 2019·Expert Opinion on Therapeutic Targets·Devon WattsFlavio Kapczinski
May 25, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Vivian Binder NeisAna Lúcia S Rodrigues
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May 14, 2020·Neurotoxicity Research·Gislaine OlescowiczAna Lúcia S Rodrigues
May 8, 2019·Neurotoxicology·Nandkishor Ramdas KotagaleNazma Najirahmad Inamdar

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