Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats

Abstract

This study investigated the role of neuroinflammation in a lipopolysaccharides (LPS)induced cognitive dysfunction model in rats using an antioxidant, α-glycosyl isoquercitrin (AGIQ). Sixweek-old rats were dietary treated with 0.5% (w/w) AGIQ for 38 days, and LPS at 1 mg/kg body weight was administered intraperitoneally once daily on Days 8 and 10. On Day 11, LPS alone increased or tended to increase interleukin-1β and tumor necrosis factor-α in the hippocampus and cerebral cortex. Immunohistochemically, LPS alone increased the number of Iba1 + and CD68 + microglia, and GFAP + astrocytes in the hilus of the hippocampal dentate gyrus (DG). AGIQ treatment decreased or tended to decrease brain proinflammatory cytokine levels and the number of CD68 + microglia in the DG hilus. In the contextual fear conditioning test during Day 34 and Day 38, LPS alone impaired fear memory acquisition, and AGIQ tended to recover this impairment. On Day 38, LPS alone decreased the number of DCX + cells in the neurogenic niche, and AGIQ increased the numbers of PCNA + cells in the subgranular zone and CALB2 + hilar interneurons. Additionally, LPS alone decreased or tended to decrease the number of synaptic plasticity-related FOS + and COX2 + granule cells and AGIQ recovered them. The results suggest that LPS administration induced acute neuroinflammation and subsequent impairment of fear memory acquisition caused by suppressed synaptic plasticity of newborn granule cells following disruptive neurogenesis. In contrast, AGIQ exhibited anti-inflammatory effects and ameliorated LPS-induced adverse effects. These results suggest that neuroinflammation is a key factor in the development of LPS-induced impairment of fear memory acquisition.

Effect of 2-Week Naringin Supplementation on Neurogenesis and BDNF Levels in Ischemia–Reperfusion Model of Rats

“…We also looked at IL-10 levels as part of the research to determine the inflammatory process, but the data should not be used here (unpublished information). However, in studies conducted with the use of different flavonoids other than naringin, it has been reported that neurogenesis increases by suppressing neuroinflammation (Rostamian et al, 2023 ; Tang et al, 2023 ).…”