Citation

Jiang B, Song L, Wang CN, Zhang W, Huang C, Tong LJ. Int. J. Neuropsychopharmacol. 2016; 19(9): 1-13.

Copyright

(Copyright © 2016, Cambridge University Press)

DOI

10.1093/ijnp/pyw046

PMID

unavailable

Abstract

BACKGROUND: Depression is a serious psychiatric disorder that easily causes physical impairments and a high suicide rate. Monosialotetrahexosylganglioside is a crucial ganglioside for the central nervous system and has been reported to affect the function of the brain derived neurotrophic factor system. This study is aimed to evaluate whether monosialotetrahexosylganglioside has antidepressant-like effects.

METHODS: Antidepressant-like effects of monosialotetrahexosylganglioside were assessed in the chronic social defeat stress model of depression, and various behavioral tests were performed. Changes in the brain derived neurotrophic factor signaling pathway after chronic social defeat stress and monosialotetrahexosylganglioside treatment were also investigated. A tryptophan hydroxylase inhibitor and brain derived neurotrophic factor signaling inhibitors were used to determine the antidepressant mechanisms of monosialotetrahexosylganglioside.

RESULTS: Monosialotetrahexosylganglioside administration significantly reversed the chronic social defeat stress-induced reduction of sucrose preference and social interaction in mice and also prevented the increased immobility time in the forced swim test and tail suspension test. In addition, monosialotetrahexosylganglioside completely ameliorated the stress-induced dysfunction of brain derived neurotrophic factor signaling cascade in the hippocampus and medial prefrontal cortex, 2 regions closely involved in the pathophysiology of depression. Furthermore, the usage of brain derived neurotrophic factor signaling cascade inhibitors, K252a and anti-brain derived neurotrophic factor antibody, each abolished the antidepressant-like effects of monosialotetrahexosylganglioside, while the usage of a serotonin system inhibitor did not.

CONCLUSIONS: Taken together, our findings suggest that monosialotetrahexosylganglioside indeed has antidepressant-like effects, and these effects were mediated through the activation of brain derived neurotrophic factor signaling cascade. © The Author 2016.

Language: en

Keywords

adult; social interaction; Depression; male; depression; hippocampus; Hippocampus; controlled study; antidepressant agent; serotonin release; fluoxetine; priority journal; drug mechanism; signal transduction; neuropathology; nonhuman; mouse; drug effect; animal experiment; animal model; Article; brain derived neurotrophic factor; tryptophan hydroxylase; sugar intake; antidepressant activity; tail suspension test; forced swim test; medial prefrontal cortex; Chronic Social Defeat Stress; fenclonine; ganglioside GM1; immobility; k 252a; Medial Prefrontal Cortex; oxygenase inhibitor; social interaction test; sucrose preference test