Fast Green FCF Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior and Downregulates TLR4/Myd88/NF-κB Signal Pathway in the Mouse Hippocampus

Abstract

Depression is a common neuropsychiatric disorder and new anti-depressive treatments are still in urgent demand. Fast Green FCF, a safe biocompatible color additive, has been suggested to mitigate chronic pain. However, Fast green FCF’s effect on depression is unknown. We aimed to investigate Fast green FCF’s effect on lipopolysaccharide (LPS)-induced depressive-like behavior and the underlying mechanisms. Pretreatment of Fast green FCF (100 mg/kg, i.p. daily for 7 days) alleviated depressive-like behavior in LPS-treated mice. Fast green FCF suppressed the LPS-induced microglial and astrocyte activation in the hippocampus. Fast green FCF decreased the mRNA and protein levels of Toll-like receptor 4 (TLR4) and Myeloid differentiation primary response 88 (Myd88) and suppressed the phosphorylation of nuclear factor-κB (NF-κB) in the hippocampus of LPS-treated mice. Fast green FCF also downregulated hippocampal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, but did not alter the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus of LPS-treated mice. The molecular docking simulation predicts that Fast green FCF may interact with TLR4 and interrupt the formation of the TLR4-MD2 complex. In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms.

Phytomedicine-Based Potent Antioxidant, Fisetin Protects CNS-Insult LPS-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment

“…Previously, studies have shown that the interaction of CD14, a glycosylphosphatidylinositol-anchored monocytic antigen, with TLR4 is an early event of neuroinflammation signaling activation [46]. Additionally, upon LPS binding, CD14 associates with the extracellular domain of TLR4, which in turn activates the TLR4 intracellular domain-mediated signaling complex including MyD88, IRAK, and TRAF, leading to downstream signal transduction through NF-κB-mediated inflammatory cascades [47,48].…”

Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression

“…The RT-PCR analysis was performed as previously described (Yang et al, 2019). Four weeks after CUMS, our control mice were deeply anesthetized with an overdose of sodium pentobarbital (150 mg/kg i.p.)…”

Knockout of NPFFR2 Prevents LPS-Induced Depressive-Like Responses in Mice

“…However, after the resolution of sickness behavior, the rodents persistently display depressive-like behaviors, indicated by increased immobility in the forced swimming test (FST) and anhedonia in the sucrose preference test (SPT) [ 36 , 38 , 39 , 40 ]. It has been proposed that neuroinflammation-related activation of TLR4/Myd88/NF-κB signaling pathway in the hippocampus might play an important role in partially mediating LPS-induced depression-like behaviors [ 41 , 42 ]. Several reports have supported the notion that inhibiting cytokine release and/or interrupting the TLR4/Myd88/NF-κB signaling pathway may be effective in reducing the magnitude of LPS-induced depression-like behavior, but not LPS-induced sickness [ 42 , 43 , 44 ].…”

“…It has been proposed that neuroinflammation-related activation of TLR4/Myd88/NF-κB signaling pathway in the hippocampus might play an important role in partially mediating LPS-induced depression-like behaviors [ 41 , 42 ]. Several reports have supported the notion that inhibiting cytokine release and/or interrupting the TLR4/Myd88/NF-κB signaling pathway may be effective in reducing the magnitude of LPS-induced depression-like behavior, but not LPS-induced sickness [ 42 , 43 , 44 ]. Taken together, the results of these studies have two major implications.…”