Effects Of Enriched Environment On Aging-related Changes Of Cognition And Hipppocampal Synaptic Plasticity Related Proteins In Maternal Mice Exposed To Lipopolysaccharide During Pregnancy

Background:The mechanisms of aging-related cognitive impairment and effective treatment methods remain to be resolved.Cognitive impairment is affected by many adverse factors such as stress,infection,and poor pregnancy,whereas enriched environment(EE)may improve animal health.Evidence suggests that synaptic plasticity is the basic neural mechanism of learning and memory in the central nervous system,particularly important for cognitive function.The changes of synaptic plasticity related protein levels can affect cognitive function by affecting synaptic plasticity.Our previous studies have shown that exposure to bacterial lipopolysaocharide(LPS)in late pregnancy aggravates the impairment of learning and memory in maternal aged mice,but it is unknown whether EE alleviates this change and whether some important synaptic plasticity related proteins such as post-synaptic densities95(PSD-95),glutamate AMPA receptor 1(GluA1),and Homer1b/c proteins are involved in these changes.Objectives:To investigate the effects of LPS exposure during pregnancy on the aged-related cognitive function in CD-1 maternal mice and the improved effect of EE on it,assess the aging-related changes in the expression of PSD-95,GluA1 and Homer1b/c proteins in hippocampus and the effects of LPS and EE,and explore the correlations between cognitive function and synaptic plasticity related proteins in hippocampus.Methods:Pregnant CD-1 mice were randomly injected intraperitoneally injected with LPS(50 μg/kg)or the same volume of saline(control group,CON)every day at gds 15-17.The female mice gave birth normally and were separated from their offspring 21 days after birth.Then these mothers receiving LPS were randomly given EE treatment(LPS-EE group)or no any treatment(LPS group).The mice were evaluated far spatial learning and memory using the Morris Water Maze(MWM)task at 6-and 18-month-old.Western blotting was used to detect the content of synaptic plasticity related proteins in the hippocampus of maternal mice.Results:(1)Spatial learning and memory for MWM task① Age effect Compared to the 6-month control group,the swimming distance in the 18-month control group was significantly longer[F(1,10)=20.781,P<0.01],and the percentage of swimming distance within the target quadrant were significantly lower(t=2.860,P=0.017).②Treatment effect Here were no significant differences in the learning swimming distance and the percentage of swimming distance within the target quadrant among the three groups at the age of 6 months[F(2,15)=0.313,P=0.736;F(2,15)=0.404,P=0.675].There were significant differences in swimming distance in the learning phase among the three groups at the age of 18 months[F(2,15)=40.745,P<0.01].In detail,the swimming distances of the 18-month LPS group were significantly longer than the control and LPS-E groups(Ps<0.01).The LPS-E group was also significantly longer than the control group.In memory phase,there were significant differences in the percentage of swimming distance within the target quadrant among the three groups[F(2,15)=10.372,P=0.001].The percentage of swimming distance within the target quadrant in the LPS goup were significantly lower than those of control and LPS-E groups(P<0.01,P=0.028).(2)synaptic plasticity related proteins① Age efect Compared to the 6-month control group,the hippocampal PSD-95,Homer1b/c and GluA1 levels in 18-month control group were significantly lower[t=24.159,P<0.01;t=13.549.P<0.01;t=18.404,P<0.01].②Treatment effect There were no significant differences in synaptic plasticity related protein levels in the hippocampus among the three groups at the 6 months of age[F(2,15)=0.509,P>0.05;F(2,15)=1.167,P>0.05;F(2,15)=0.068,P>0.05].There were significant diffferences in hippocampal levels of synaptic plasticity related proteins among the three groups[F(2,15)=322.940,P<0.01;F(2,15)=321.431,P<0.01;F(2,15)=392.495 P<0.01].Pairwise comparison showed that the LPS and LPS-E groups were significantly lower than the control group(Ps<0.01),while the LPS group was significantly lower than the LPS-E group(P<0.01).(3)Relationship between synaptic plasticity related proteins and cognitionPearson correlation analysis showed the hippocampal levels of PSD-95,GluA1 and Homer1b/c correlated negatively with the swimming distance in the learning phase(Ps<0.05)and were positively with the percentage of swimming distance within the target quadrant in the memory phase(Ps<0.05).Conlusion:(1)Old CD-1 mice had the learning and memory impairment and the decrease of the synaptic plasticity related proteins(PSD-95.Homer1b/c and GluA1).(2)Exposure to LPS in the late pregnancy aggravated the age-related impairment of learning and memory and decreased the level of synaptic plasticity related proteins,and EE improved these changes.(3)The levels of synaptic plasticity related protein decreased in the hippocampus may be associated with learning and memory impairment.