Effects Of Exposures To Inflammation In Embryonic Period And Environmental Stimulation During Puberty On Age - Related Changes Of Behaviors In The CD-1 Mice

BackgroundEvidence suggests many adult diseases are related to the interference during early human life or prenatal exposure to adverse factors,which mechanism involving the interaction of genes and environment.Our preliminary work shows that exposure to bacterial lactobacillus lipopolysaccharide?LPS?in pregnancy mothers can accelerate changes of aging-related behavioral in their offspring mice.But it is unclear that if their offspring re-exposing to environmental stimulations agin can accelerate or alleviate age-related cognitive decline.ObjectiveTo investigate the effects of combined environmental stimulations in early life?embryonic or adolescent?on age-related behaviors in CD-1mice.MethodsThe pregnant mice received an intraperitoneal injection of LPS?50?g/kg?or normal saline during gestational day 15–17.The offspring were separated from their mothers at age of 21 days,and randomly divided into five groups:LPS-stressed group?L-S?,LPS-enriched group?L-E?,LPS-control group?L-C?,NS-stressed group?N-S?and NS-control group?N-C?.The L-S and the N-S received daily one way of stresses?tail suspension,restraint,illumination or fasting?,four days of a cycle and a total of seven cycles.The mice in L-E were housed in a big cage and enjoyed a novel objects weekly until the end of behavioral tests.When the mice respectively grown to 3 months and 15 months of age,systematic behavior tests were completed,including spontaneous exploration?open field?,anxiety tasks?open field,black–white alley?,and learning and memory?novel location recognition,Morris water maze?.ResultsExplore behavior.In the open field,compared to the young N-C,squares crossed in the middle-aged N-C significantly reduced.In the 3-month mice,olny the L-S had less squares crossed than the N-C?Ps<0.05?.In the 15-month mice,the L-S had significantly less squares crossed than the L-C,L-E,N-S and N-C.so did the L-C and N-S than the N-C?Ps<0.05?.Anxious behaviors.Compared to the young N-C,the middle-aged N-C significantly increased latency and peripheral time in the open field and latency and black-end time in the black-white alley?Ps<0.05?.At age of 3 months,the L-S had significantly longer latency and peripheral time in the open field than the L-E and N-C.the L-C had significantly longer latency than the N-C,and the L-S had significantly longer peripheral time than the N-S.In the black-white alley,the L-S had significantly longer latency than the L-E and N-C,so did the L-C has than the N-C.For the black-end time,the L-S were significantly longer than the N-S and N-S,and the L-E were significantly longer than the N-C?Ps<0.05?.At the age of 15 months,in the open field,the L-S had significantly longer latency and peripheral time than the L-C,N-S,L-E and N-C.The L-C had significantly longer latency than the L-E and N-C,so did the N-S has than the N-C.The L-C had significantly longer peripheral time than the N-C.In the black-white alley,the L-C and N-S had significantly longer latency and black-end time than the N-C,the L-S had significantly longer latency than the L-E and N-C;the L-S had significantly longer black-end time than the L-C,N-S,L-E and N-C?Ps<0.05?.Novel location recognition task.Compared to the young N-C,the middle-aged N-C had significantly smaller preferential index?PI?for 10-min(PI_10min)or 24-h(PI_24h)delay.In the 3-month mice,there were no significantly differences in the PI_10min and PI_24h among five groups?Ps>0.05?.In the 15-month mice,the L-S had significantly smaller PI_10min and PI_24h than the N-S,L-E and N-C,so did the L-C,N-S and L-E have than the N-C?Ps<0.05?.Morris water maze task.In the learning and memory phases,the swimming distance progressively declined over days,indicating these mice were able to learn or memorize the task?Ps<0.001?.The middle-aged N-C had significantly longer swimming distance in the learning phase and lower percentage of distance in the target quadrant in the memory phase than the young N-C?Ps<0.05?.At 3-month old,the L-S,L-C and N-S had significantly lower percentage of distance in the target quadrant than N-C?Ps<0.05?.At 15-month old,in the learning phase,the L-S had significantly longer swimming distance than the L-C,N-S,L-E and N-C,the L-C had significantly longer distance than the N-S,L-E and N-C,the N-S had significantly longer distance than the L-E and N-C.So did the L-E than the N-C?Ps<0.05?.In the memoring phase,the L-S had significantly lower percentage of distance in the target quadrant than N-S,L-E and N-C.So did the L-C than the N-C?P<0.05?.ConclusionsBoth prenatal exposure of inflammation and adverse environmental stimulus during puberty could worsen age-related cognitive behaviors,and synergistic effect are observed when combination of two stimulations.On the other hand,the treatment of enriched environment cross the adults could alleviate this adverse effect.