Abstract
Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.
Highlights
Inflammation is a biological response initiated by various types of tissue upon sensing any foreign particle; the purposes of the response are to prevent further tissue harm and injury, to clear and repair damaged tissue, and to eliminate pathogenic elements
These results demonstrated that quercetin reversed the detrimental effect of LPS and significantly improved memory performance
To analyze the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (Iba-1), we found through western blotting that LPS treatment significantly increased the expression of these two proteins in the adult mouse cortex and hippocampus compared to the control group of mice
Summary
Inflammation is a biological response initiated by various types of tissue upon sensing any foreign particle; the purposes of the response are to prevent further tissue harm and injury, to clear and repair damaged tissue, and to eliminate pathogenic elements. Tissue damage and systemic inflammation lead to glial cell activation, which releases inflammatory mediators and induces inflammatory diseases in the brain, such as meningitis and multiple sclerosis, as well as non-inflammatory diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) (Qin et al, 2007; Di Filipopo et al, 2010; Tajuddin et al, 2014). Numerous studies have reported that the activation of glial cells releases harmful mediators such as reactive oxygen species (ROS), nitric oxide, cytokines and inflammatory mediators, which lead to neuroinflammation-mediated neuronal degeneration (Di Filippo et al, 2008; Chen W.W. et al, 2016; Kempuraj et al, 2016, 2017). Various in vitro and in vivo studies have reported that LPS activates glial cells, leading to neuroinflammation followed by neurodegeneration (Johansson et al, 2014; Qin et al, 2015; Khan et al, 2017)
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