Effects of ginkgo diterpene lactone meglumine on learning and memory in old mice and its mechanisms

Abstract

Objective To study the effects of diterpene ginkgolides meglumine injection (DGMI) on memory impairment, activation of microglia and astrocytes and inflammatory cytokines in aged mice. Methods Twenty aged mice (22 months old) were randomly divided into two groups: aged mouse group(n=10) and DGMI group(n=10). Another 10 mice (2 months old) were selected as young mouse control group. The mice in DGMI group were received 5 mg/kg DGMI per day by tail vain injection for 4 weeks.The mice in the other two groups were received the same amount normal saline for 4 weeks. The Morris water maze was used to evaluate the function of spacial learning and memory after administration of drugs. The expression of CD11b, GFAP, IL-1β, IL-6, TNF-α and NFκB in mice brain hippocampus were detected by Western blot. Results (1) The escape latency time of aged mouse group was significantly longer than that of young mouse control group from the 2nd day to the 7th day(P<0.01). The times of platform crossing, time and distance in target quadrant of aged mouse group were significantly shorter than those of young mouse group (all P<0.01). Compared with aged mouse group, DGMI significantly reduced the escape latency time of DGMI group (P<0.01). DGMI increased the times of platform crossing, time and distance in target quadrant of aged mouse group (P<0.01). (2) The expressions of CD11b, GFAP in young mouse control group, aged mouse group and DGMI group were as follows respectively: CD11b: (1.036±0.023), (1.757±0.046), (1.214±0.024); GFAP: (1.022±0.071), (1.344±0.021), (1.086±0.073). DGMI reduced the expression of CD11b and GFAP in hippocampus compared with aged mouse group (t=5.556, P<0.01; t=5.484, P<0.01). (3) The expressions of IL-1β, IL-6, TNF-α and NFκB in young mouse control group, aged mouse group and DGMI group were as follows respectively: IL-1β: (1.003±0.057), (2.062±0.105), (1.182±0.084); IL-6: (1.018±0.024), (1.583±0.052), (1.152±0.031); TNF-α: (1.021±0.054), (1.449±0.053), (1.211±0.036); p-NFκB: (1.052±0.034), (1.782±0.113), (1.158±0.066). DGMI reduced the expression of p-NFκB(t=6.547, P<0.01) and pro-inflammatory cytokines including IL-1β(t=8.513, P<0.01), IL-6(t=3.421, P<0.01) and TNF-α(t=5.562, P<0.01) in hippocampus compared with aged mouse group. Conclusion DGMI can improve the ability of learning and memory in aged mice. The mechanism may be related with inhibiting activity of microgliosis, astrocytosis, NFκB and neuroinflammaton. Key words: Diterpene ginkgolides meglumine injection; Aged mice; Learning and memory; Neuroinflammation