Journal of Hebei Medical University ›› 2023, Vol. 44 ›› Issue (6): 629-634,639.doi: 10.3969/j.issn.1007-3205.2023.06.002

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The mechanism of GV-971 improving cognitive impairment and reducing neuroinflammation in Alzheimer′s disease

  

  1. Department of Neurology, People′s Hospital of Pudong New Area, Shanghai 201200, China

  • Online:2023-06-25 Published:2023-06-29

Abstract: Objective To investigate the mechanism of the effect of oral administration of sodium oligomannate capsules (GV-971) on cognition and neuroinflammation in Alzheimer′s disease (AD) mice. 
Methods Female APP/PS1 mice with Alzheimer′s disease were purchased and treated with oral GV-971. The cognitive function of mice was tested by Morris water maze test and Y-maze test. Amyloid β-protein (Aβ) deposition was detected by thioflavin S staining, and the levels of inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-10 in the brains of each group of mice were measured by enzyme-linked immunosorbent assay (ELISA) kits. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels of BACE1 mRNA and protein in the brain tissue of mice, respectively. 
Results The escape latency of the healthy group and the control group showed a decreasing trend over time, with the healthy group showing a more significant trend than the control group. The escape latency of the treatment group showed a trend of initially shortening, then prolonging, and then shortening over time. There was a significant difference in the interaction between groups, time points, and time points between groups (P<0.05). The percentage of time spent in the target quadrant in the treatment group was less than that in the healthy group and the control group (P<0.05). The accuracy of Y-maze passage in the treatment group was lower than that in the healthy group and control group (P<0.05). Compared with the healthy group, the percentage and area of Aβ plaques in cerebral cortex and hippocampus the control group were increased (P<0.05), which, however, were decreased in the treatment group, as compared with the control group, (P<0.05). The ELISA results showed that compared with the healthy group, inflammatory cytokines IL-1β and TNF-α levels in brain tissue of mice in the control group mice were increased, while the IL-10 levels were decreased (P<0.05). Compared with the control group, IL-1β and TNF-α levels in the treatment group were decreased, while the IL-10 levels were increased (P<0.05). Compared with the healthy group, the mRNA and protein levels of BACE1 in the brain tissue of mice in the control group were increased (P<0.05). Compared with the control group, the mRNA and protein expression of BACE1 in the brain of mice in the treatment group was decreased (P<0.05). 
Conclusion GV-971 decreased the expression of BACE1 in the brain tissue, improved cognitive impairment and reduced neuroinflammation in AD mice. 

Key words: Alzheimer′s disease, sodium oligomannate, neuroinflammation