Effects Of Inflammation In Late Pregnancy On Sleep And Behaviors In Aged Mice And The Alleviating Effect Of Enriched Environment

BackgroundWith the increasing age,sleep quality and cognitive ability gradually decline.Similarly,the emotional state also changes.These age-related changes can be affected by many factors,such as pregnancy,infection,psychosocial stress,etc.In pregnant women,the endocrine and immune systems of the body will undergo significant changes,so they were vulnerable to infection or inflammation and other adverse factors.Our previous studies have shown that exposure to inflammatory environment caused by bacterial lipopolysaccharide?LPS?during the late pregnancy accelerates the decline of learning and memory and the increase of anxiety in the elderly.And the current evidences suggest that a decline in cognitive function and an increase in anxiety levels are usually accompanied by a decline in sleep quality.However,it is unknown whether exposure to inflammation in the late pregnancy exacerbates the decline of sleep quality in the elderly,and whether the enriched environment has a protective effect on these behavioral changes has not been reported.ObjectiveTo explore the effects of inflammation exposure in late pregnancy on sleep and behavior in the elderly mice and the alleviating effect of enriched environment.MethodsPregnant CD-1 mice were randomly received intraperitoneally LPS?50?g/kg/d,30 mice?or equal amount of saline?15 mice,control group?during 15th�17th days of gestation.All the animals were delivered normally and fed under normal conditions,but the LPS treatment group was randomly divided into enriched environment group?15 mice,LPS-E group?and no treatment group?15 mice,LPS group?.The animals were raised to 18 months old,and the number of animals in each group was 10,meanwhile another 3-month-old female rats?10 mice?were used as the young control group to complete the follow experiment.Behavior experiments include:sleep detection?behavior-based sleep monitoring system?;Learning and memory ability test?Morris water maze and novel object recognition task?;Free exploration activities and anxiety behavior detection?open-field experiment,black-and-white alley and elevated cross maze?.Results1. Sleep parameters:?1?Age effect:Compared with the 3-month-old control group,the total sleep time?P<0.001?,times?P=0.023?and index?P<0.001?of the 18-month-old control group were significantly lower.?2?Treatment effect:Compared with the elderly control group,the total sleep time,sleep frequency and sleep index were significantly lower in LPS and LPS-E groups?Ps<0.001?,and single sleep time also was lower in LPS group?P<0.001?;Compared with the LPS-E group,the total sleep time?P<0.001?,times?P=0.001?,index?P<0.001?and single sleep time?P<0.001?were significantly lower in the LPS group.2. Morris water maze:?1?Age effect:During the learning period,the swimmingdistance of 3-month-old and 18-month-old control mice decreased with the increase of days?P<0.001?.Compared with the 3-month old mice,the swimming distance of the18-month old control group was significantly longer?P<0.001?.During the memory period,the percentage of swimming distance in the target quadrant of the 18-month-old control group was significantly lower than that in 3-month-old mice?P=0.001?.?2?Treatment effect:During the learning period,the swimming distance of the three groups also decreased with the increase of days in the elderly mice?P<0.001?.The swimming distance of LPS and LPS-E group was significantly longer than that of the control group?Ps<0.001?,while the swimming distance of LPS group was significantly longer than that of LPS-E group?P<0.001?.During the memory period,the percentage of swimming distance in the target quadrant of the LPS group?P<0.001?and the LPS-E group?P=0.028?was significantly lower compared with the control group,while the LPS group was lower than that of the LPS-E group?P=0.006?.3. Novel object recognition task:?1?Age effect:Compared with the young control group,the PI₁and PI₂in the elderly control group were significantly lower?Ps<0.001?.?2?Treatment effect:Compared with the elderly control group,PI₁in the LPS-E group was lower?P=0.017?,and both PI₁and PI₂in the LPS group were significantly lower,too?Ps<0.001?.Compared with the LPS-E group,the PI₁and PI₂were significantly lower in the LPS group?Ps<0.001?.4. Free exploration behavior:?1?Compared with the youth control group,the gridnumber and upright times of the elderly control group in the open span were smaller?Ps<0.05?,and the number of upright positions in the elevated cross maze were smaller,too?P<0.001?.?2?At the age of 18 months,compared with the elderly control group,both the upright times and cross grid numbers in the open field in LPS and LPS-E groups were significantly smaller?Ps<0.001?,and the number of upright in the elevated cross maze was significantly smaller?P<0.001?.Compared with the LPS-E group,the number of upright times and cross grid in the open field were significantly smaller in the LPS group?Ps<0.05?,and the number of upright in the elevated cross maze was significantly smaller in the LPS group?P<0.001?.5. Anxious behavior:?1?Compared with the youth control group,the incubation period and the total surrounding time of the open field were significantly longer,the incubation period of the black-and-white alley and the dark lane time were significantly longer,the incubation period of the elevated cross maze was longer,but the time of the open arm was less?Ps<0.05?.?2?At the age of 18 months,compared with the elderly control group,the incubation period of open field in the LPS and LPS-E groups were longer,and the total peripheral time of the LPS group was longer;the incubation period and the time of black lane were significantly longer;the incubation period of elevated cross maze was longer and the opening arm time was less?Ps<0.05?.Compared with the LPS-E group,the LPS group had longer incubation period in the open field,longer incubation period for black-and-white alley,longer incubation period of the elevated cross maze,and less time in the open arm?Ps<0.05?.6. Sleep and the ability of learning and memory:The total sleep time,frequency,index,time/times were negatively correlated with the learning swimming distance?Ps<0.001?,positively correlated with the percentage of swimming distance in the target quadrant of water maze?Ps<0.001?,and positively correlated with the PI₁and PI₂of novel object recognition task?Ps<0.001?.7. Sleep and anxiety:Sleep parameters were negatively correlated with the latencyand total peripheral time in the open field?Ps<0.001?;negatively correlated with the latency and black lane time in the black and white lane?Ps<0.001?;negatively correlated with the latency in the elevated cross maze?Ps<0.001?;and positively correlated with the time of open arm?Ps<0.001?.Conclusions?1?Exposure to inflammation in the late pregnancy resulted in decreased sleep quality,increased anxiety behavior,decreased spontaneous exploration behavior and decreased learning and memory ability in aged CD-1 mice.?2?In mice exposed to inflammation in the late pregnancy,sleep quality was reduced in the elderly,learning and memory decline was delayed,and anxiety were increased,but enriched environment significantly improved this phenomenon.?3?Decreased sleep quality in aged mice was associated with changes in anxiety and learning and memory.