Effects Of Exposure To Inflammation And Psychosocial Stress In The Early Of Life On Age-Related Changes Of Behaviors And Hippocampal Staufen Protein In CD-1 Mice

Background: With the increasing aged populations,age-related memory impairment(AAMI)has become a major concern for the older and elderly.However,the triggers and the mechanism underlying its maintenance remain unclear.The well-known " fetal origins of adult diseases " believes that many diseases in adults are often associated with direct or indirect effects of early environmental changes.Studies have found that exposure to early inflammation significantly increases the susceptibility to AAMI.At the same time,with the increasingly fierce competition in modern times,the effects of the psychological and social environment on people's cognitive function has also gradually drew people's attention.Staufen(Stau)protein is a double-stranded RNA-blinding protein(RBP)ubiquitously expressed in neuronal cell bodies,which is implicated in dendritic mRNA transport,critically linked to modulate synaptic plasticity and cognitive performance.However,there are few studies on the effects of early inflammation and social environment exposure on cognitive function or RBP and neurobiology of middle-aged and elderly people.Objective: To explore effects of exposure to inflammation and psychosocial stress in the early of life on age-related changes of behaviors and hippocampal Staufen protein in the middle-aged CD-1 mice.Methods: Pregnant CD-1 mice were randomly divided into LPS-group and control-group.LPS-group received intraperitoneally LPS(50 ?g/kg)during 15th–17th days of gestation,while the control-group received equal amount of saline.At the age of 2 months,LPS-group offspring mice were randomly constituted 3 groups: stress group,enriched environment group and no-treatment group,and simultaneously,then the control mice were randomly constituted 2 groups: stress group or no-treatment group.Finally,five groups were obtained: LPS-stress group(LPS-S),LPS-enriched-environment group(LPS-E),LPS no-treatment group(LPS),control-stress group(CON-S)and control no-treatment group(CON).The stress group randomly selected a stress method from restraint,suspension,nighttime illumination and nocturnal fasting for 28 days.Enriched environmental treatment group were reared in large cages to promote social activities and group activities,with changing types or shapes of novel toys in the cage every week to enhance the novelty of the novel environment.The entire process was maintained until the end of the Morris water maze experiment.3-month(young)and 15-month(middle-aged)CD-1 mice were used(5 males)per group.The ability of spatial learning and memory was evaluated using the Morris water maze test,and the expression of Stau protein was examined using immunohistochemical or Western blotting methods.Correlation analysis was performed between behavioral test and protein content.Results: ?The effect of age: Compared to the 3-month-old CON mice,the learning swimming distance and hippocampal Stau protein content in the 15-month-old CON were significantly increased(Ps < 0.05),and the memory percentage of swimming distance was significantly decreased(P < 0.05).?The effect of treatment:(1)In the 3-month-old mice,there were significant differences in the learning swimming distance,memory percentage of swimming distances and level of Stau among LPS-S,LPS,LPS-E,CON-S and CON mice(Ps < 0.05).Compared to the LPS,LPS-E,CON-S and CON mice,the LPS-S had a significant increase in learning swimming distance and Stau protein expression(Ps < 0.05),and a significantly decrease in the memory percentage of swimming distance(Ps < 0.05).In the LPS,the memory percentage of swimming distance was significantly lower than the CON(P < 0.05),and the expression level of Stau protein was significantly higher than LPS-E,CON-S,and CON(Ps < 0.05).The expression level of Stau protein in the CON was significantly lower than the other four groups(Ps < 0.05).(2)In the 15-month-old mice,there were significant differences in the learning swimming distance,memory percentage of swimming distances and level of Stau among LPS-S,LPS,LPS-E,CON-S and CON(Ps < 0.05).Compare to the other four groups,the LPS-S was the highest in the learning swimming distance and Stau protein expression(Ps < 0.05)while the memory percentage of swimming distance was the lowest(Ps < 0.05).The learning swimming distance and Stau protein level in the LPS were significantly higher than LPS-E,CON-S and CON(Ps < 0.05).Compared to the other four groups,the CON was the lowest in the learning swimming distance and Stau expression(Ps < 0.05)but the highest in the memory percentage of swimming distance(Ps < 0.05).?Stau and cognition:The hippocampal Stau protein in the 3-month-old CON-S,LPS and LPS-E mice,as well as 15-month-old LPS-S,LPS and CON mice were positively correlated with the learning swimming distance.The hippocampal Stau protein in the 3-mouth-old CON and the 15-mouth-old LPS-S and LPS-E were negative correlated with the memory percentage of swimming distance(Ps < 0.05).Conclusions: Exposure to inflammation and psychosocial stress in the early of life can accelerate the AAMI(both factors have a synergistic deterioration effect,and the effect of inflammatory is worse),but the enriched environment can weaken this effect.meanwhile the increased hippocampal Stau level may participate in the impairment of spatial learning and memory.