| Background:Age-associated cognitive decline has become a prominent problem affecting health,but its exact mechanism is not clear.Studies have shown that hippocampal synaptic plasticity is essential for learning and memory,and changes in the expression of synaptic plasticity-related proteins can lead to cognitive impairment by affecting synaptic plasticity.As we all know,the perinatal period is a critical period in an adult woman’s life.Stress generated during this period（such as mother-infant separation,premature fetal death）may have adverse effects on neurological function,especially in the hippocampus.The maternal separation is one of the common post-natal stress factors.Studies have shown that maternal separation may lead to impaired spatial learning and memory in offspring.However,whether maternal separation affects maternal cognition and hippocampal synaptic plasticity-related proteins remains unclear.Objective:To investigate the effects of maternal separation on age-related cognition and the expression of synaptic plasticity related proteins PSD95 and Arc and their mRNA in hippocampus of aged S AMP8 maternal mice.Methods:The pregnant mice were randomly divided into the control group（CON）and the maternal separation group（MS）.After the pregnant mice in the separated group gave birth,mothers were separated from their pups for 3h（8:00 a.m.to 11:00 a.m）once a day from postpartum day 7 to 16.Control mothers were kept with their pups until weaning.All pups were weaned 21 days after birth,and maternal mice were housed in single cages.Finally,the maternal mice were divided into two different age groups of 3 and 9 months,four groups were obtained:3-CON group,3-MS group,9-CON group and 9-MS group.When maternal mice were 3 months old and 9 months old,6 maternal mice were randomly selected from each group and placed in the Morris water maze to evaluate the spatial learning and memory ability of the female mice.Finally,real-time PCR and Western blot were used to measure the synaptic protein content and mRNA-related levels in the hippocampus.Results:1、Morris water maze（1）Age effect:Compared with 3-CON group,the swimming distance of 9-CON group was longer than that of 3-CON group during learning period（P<0.05）.In memory period,the percentage of distance in 9-con target quadrant decreased（P<0.05）（2）Treatment effect:There was no significant change in percentage of swimming distance and target quadrant distance between the 3-MS group and the 3-CON group in both learning and memory periods（Ps>0.05）.Compared with the 9-CON group,the swimming distance in the 9-MS group was significantly longer in learning period（P<0.05）,and the percentage of target quadrant distance in memory period was significantly decreased（P<0.01）.2、PSD-95,Arc protein and their mRNA related levels（1）Age effect:Compared with female rats in 9-CON group and 3-CON group,the protein levels of PSD-95 and Arc and their mRNA transcription levels were significantly decreased in 9-CON group（P<0.05）.（2）Treatment effect:Compared with 3-CON group,PSD-95 and Arc proteins and their mRNA transcription levels in 3-MS group were significantly decreased（P<0.05）.Compared with 9-CON group,the mRNA transcription levels of PSD-95 and Arc in 9-MS group were significantly decreased（P<0.05）.3、Correlation between PSD-95,Arc protein and their mRNA levels and behavioral performanceIn 3-month-old mice,the correlation levels of PSD-95 and Arc protein and their mRNA in hippocampus of 3-CON group and 3-MS group were not correlated with the percentage of swimming distance in water maze or the percentage of target quadrant distance in memory period（P>0.05）.In 9-month-old mice,the correlation levels of PSD-95 and Arc proteins and their mRNA in 9-CON and 9-MS groups were negatively correlated with swimming distance in learning period（P<0.05）,and positively correlated with percentage of target quadrant distance in memory period（P<0.05）.Conclusions:（1）The stress experience caused by the maternal separation had little effect on the learning and memory of maternal mice in youth,but had a negative effect on the memory in old age;（2）Aging and maternal separation can reduce the expression of synaptic plasticity related proteins PSD-95 and Arc,leading to age-related cognitive impairment.These two factors have a synergistic effect,and the effect of maternal separation is stronger than aging;（3）The decrease of synaptic plasticity related proteins PSD-95 and Arc may be related to learning and memory. |
PDF Full Text Request