Effects of ginkgo diterpene lactone meglumine on learning and memory in old mice and its mecha-nisms / 中华行为医学与脑科学杂志

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 ex-pression of CD11b,GFAP,IL-1β,IL-6,TNF-α and NFκB in mice brain hippocampus were detected by West-ern 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 quad-rant 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 expres-sion 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 mecha-nism may be related with inhibiting activity of microgliosis,astrocytosis,NFκB and neuroinflammaton.