Effects of lithium chloride on open-field behaviors in fragile X mental retardation 1 gene knockout mice

Abstract

Objective To study the effects and potential mechanisms of lithium chloride on openfield behaviors of fragile X mental retardation 1 gene (FMR1) knockout mice (KO mice).Methods 4-weekold KO mice (n=90) and their wild type counterparts (WT mice,n=90) were,by using random number table,assigned to control group (intraperitoneally injected with normal saline,n=15) and 5 treatment groups intraperitoneally injected with 30 mg/kg (n=15),60 mg/kg (n=15),90 mg/kg (n=15),120 mg/kg (n=15) and 200 mg/kg lithium chloride (n=15) for 5 consecutive days,respectively.The differences in the total length of running,total number of region crossings,and the duration and number of central region crossings of all groups were determined in open field tests.Meanwhile,Western blotting was used to observe the expression of glycogen synthase kinase3β (GSK3β) and phosphorylated glycogen synthase kinase3β (PGSK3β) in the hippocampus and cortex of KO and WT mice.Results KO mice had longer distance of movements,greater total number of region crossings,longer duration and greater number of central region crossings than WT mice (all P＜0.05).Compared with control group,administration of lithium chloride resulted in significantly reduced distance of movements,total number of region crossings,shorter duration and smaller number of central region crossings (all P＜0.05) in KO mice.Lithium chloride administration (90,120 and 200 mg/kg) was associated with shorter distance of movements and duration of central region crossings in WT mice as compared with control group (all P＜0.05).200 mg/kg,but not 30 to 120 mg/kg,lithium chloride led to reduced total number of region crossings compared with control group (75.73±5.12 vs 125.73±9.24,P＜0.05).However,lithium chloride administration was associated with a reduced number of central region crossings compared with control group (all P＜0.05).No significant difference was found in hippocampus and cortex GSK3β,but not P-GSK3β,expression between KO mice and WT mice in control group (P＞0.05).There were no significant differences in hippocampus and cortex GSK3β expression between KO mice and WT mice in lithium chloride treatment groups.Compared with control group,the cortex P-GSK3β expression was significantly higher in 120 and 200 mg/kg lithium chloride groups (both P＜ 0.05),and the hippocampus GSK3β expression was up-regulated in all lithium chloride treatment groups (all P＜0.05).In lithium chloride treatment groups,the difference in hippocampus and cortex GSK3β,as well as P-GSK3β,expression failed to reach statistical significance (both P＞0.05).Using the same dose of lithium chloride administration,hippocampus and cortex P-GSK3β (but not GSK3β) expression in KO mice was lessthan that in WT mice.Conclusion Lithium chloride ameliorates aberrant open-field behaviors of KO mice,which may be related to the up-regulation of P-GSK3β expression. Key words: Lithium chloride; Mice, knockout; Fragile X mental retardation 1 gene; Open-field behaviors ; Fragile X syndrome