| Background:It is well known that aging is often accompanied by significant cognitive impairment.This has gradually become one of the key factors affecting the quality of life of the elderly.Studies have shown that both stress and aging can lead to abnormal activation of astrocytes,especially in the hippocampus of the brain,which in turn affects the development of neurons and synapses,leading to cognitive changes.In a person’s life,early life is the most vulnerable to various stresses.Exposure to embryonic inflammation is also a frequent risk factor for early-life stress,which can adversely affect neurodevelopment and cognition.Previous studies have mainly focused on the study of stress on brain neurons,and few studies have explored the effects on astrocytes.So,what are the effects of embryonic inflammation exposure on glial fibrillary acidic protein(GFAP)and postsynaptic density protein 95(PSD-95)in the hippocampus of mice? Do these effects persist into middle-aged and elderly mice? And how are they associated with age-related cognitive changes in mice?Object:To explore the effects of fetal inflammatory exposure on age-related cognition in mice.To explore the changes of astrocyte related marker GFAP,synaptic plasticity related protein PSD-95 and their m RNA in hippocampus of mice after exposure to embryonic inflammation,and the relationship between the changes of these two proteins and cognition.Methods : In this study,appropriate amount of CD-1 mice aged 4-6 weeks were purchased and matched for male and female until reproductive age.Then pregnant mice were randomly divided into embryonic inflammation exposure group(LPS group)and control group(CON group).Mice in the LPS group received daily intraperitoneal injection of LPS(50 μg/kg)from gestational day 15 to 17,while mice in the CON group received the same volume of normal saline.Morris water maze(MWM)test was performed to evaluate the spatial learning and memory ability of the offspring mice at the age of 3 and 15 months(N=6 / group).Hippocampi were isolated on ice 15 days after the end of the ethology.The protein levels of GFAP and PSD-95 in hippocampus were detected by Western Blotting(WB),and their m RNA levels were detected by Quantitative Real Time PCR(q RT-PCR).Results:1.learning and memory ability(1)Age effect: In the CON group,the total swimming distance in the learning period of15-month-old mice was significantly prolonged(P < 0.05),and the percentage of targeted swimming distance in the memory period was significantly decreased(P <0.05).(2)Treatment effect: Compared with the CON group,the LPS group had a significantly increased total swimming distance during the learning period(P < 0.05).In the memory period,the percentage of target restricted swimming distance was significantly reduced(P < 0.05).Compared with the CON group,the LPS group had a significant increase in the total swimming distance during the learning period(P < 0.01).During the memory period,the percentage of target restricted swimming distance was significantly reduced(P < 0.01).The difference of learning and memory between LPS group and CON group at 15 months old was more obvious than that of the two groups at 3 months old.2.GFAP,PSD-95 and their m RNA levels(1)Age effect: in CON group,compared with 3 months old mice,GFAP and GFAP m RNA increased significantly(P < 0.05),PSD-95 and PSD-95 m RNA decreased significantly(P < 0.05)at 15 months old.(2)Treatment effect: compared with the data of the two groups of mice at the age of 3months,the GFAP and its m RNA in the LPS group were significantly increased(P <0.01),and the PSD-95 and its m RNA were significantly decreased(P < 0.01).Compared with the data of the two groups of mice at the age of 15 months,the GFAP and its m RNA in the LPS group were also significantly increased(P < 0.01),and the PSD-95 and its m RNA were significantly decreased(P < 0.01).3.Correlation between GFAP,PSD-95 and their m RNA levels and behavioral performance The protein and m RNA levels of the 3-month-old CON mice were not correlated with the swimming distance and the percentage of target restricted swimming distance in the water maze test(P > 0.05).In both the 3-month-old LPS group and the 15-month-old CON and LPS groups,the levels of GFAP and its m RNA were positively correlated with the total swimming distance in the learning period(P < 0.05),and negatively correlated with the percentage of targeted swimming distance in the memory period(P <0.05).The levels of PSD-95 and PSD-95 m RNA were negatively correlated with the total swimming distance in the learning period(P < 0.05),and positively correlated with the percentage of targeted swimming distance in the memory period(P < 0.05).Conclusion:Exposure to embryonic inflammation impairs the learning and memory ability of young mice,leading to an increase in GFAP and a decrease in PSD-95 in the hippocampus,and accelerates the age-related decline of learning and memory ability and the changes of two proteins in middle-aged and elderly mice,and the changes of these two proteins are related to the learning and memory ability of mice. |
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