Effects Of Psychosocial Environment And Maternal Inflammation On Age-Related Behavioral Changes In Mice: An Experimental Study

BackgroundAge-related diseases become a serious health problem along with growing in the elderly population. Importantly, brain aging and age-related neurodegenerative diseases are increasing significantly, such as Alzheimer’s disease and Parkinson’s disease. However, the mechanism is still unclear on triggering and maintaining age-related diseases, and the approaches that alleviate brain aging have not been reported. So it is particularly important to explore the potential causes and the effective treatments on the age-related diseases. In recent years, the researchers found that early human life or prenatal exposure to adverse factors could increase the incidence of adult diseases, involving the interaction of genes and environment. This view has been fully summarized in the hypothesis of “fetal origin of adult disease”. The influence of environmental factors vary widely, however, the conclusion is not entirely consistent. With the increasingly fierce competition, the psychosocial environment will significantly impact on people’s behaviors, but the effect on the aging is less research. Therefore, it will be the trend of future researches that exploring the influence of the psychosocial environment and maternal inflammatory insult during pregnancy on age-related behaviors and neurobiological indicators. Objective(1) To investigate the effect of psychosocial environment on the age-related behavioral and neurobiological changes in the CD-1 mice.(2) To investigate the effect of psychosocial environment and maternal inflammation on the age-related behavioral and neurobiological changes in mothers and their offspring. Methods(1) The different psychosocial environment models in young mice: the 2 months mice were divided into three groups, composing of the control group, stress group and enrich group. The mice in stress group were randomized to receive 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 enrich group were housed in a big cage and accepted different objects until finishing the behavioral examination. The experiments were divided into 3-, 12-, and 18-month-old groups. The 3 months mice were only used as the young control group. When the mice reached 12 and 18 months, 8 males and 8 females from each of the three groups were used for experiments. All the mice received a systematically behavioral assessment.(2) The adverse environment during pregnancy—postpartum stress model: the pregnant CD-1 mice were randomly divided into the control group and LPS group. The pregnant mice received an intraperitoneal injection of LPS(50 μg/kg) or normal saline during gestational day 15–17. On postpartum day 21, the mothers were separated from their offspring. The LPS-treatment mothers were divided into the LPS group and LPS-stressed group, and the latter were also received the stress aforementioned. When they reached 15 months old, 10 mice from each of the three groups were used for experiments. All the mice were received the same assessment.(3) Prenatal stress—postnatal psychosocial environmental changed model: the offspring mice were randomly divided into four groups, composing of the control group, LPS group, LPS-stressed group and LPS-enriched group. The LPS-stressed group and the LPS-enriched group were received the same stressed and enriched methods respectively. The behavioral tests included: sensorimotor tasks(beam walking), spontaneous exploration and anxiety tasks(open field, elevated plus maze and black–white alley), learning and memory(novel location recognition, Morris water maze).(4) After accomplishing the behavioral assessment, the mice were deeply anesthetized with halothane and were sacrificed. The hippocampus was rapidly isolated from the brain. The levels of HDAC2, PSD95, and Syn in the hippocampus were detected by Western blotting method. Results(1) The different psychosocial environment models in young mice: the 18-month old control mice displayed a significant reduction of sensorimotor and spontaneous exploration ability, novel location recognition, spatial learning and memory abilities, but the anxiety was significantly increased in the open-field and black–white alley tasks. All behavioral changes exhibited age-related characteristics. Stress could accelerate the deterioration of the behaviors in the old mice, but enriched environment could alleviate these aging effects.(2) Adverse environment during pregnancy—postpartum stress model: the behavioral scores in LPS-stressed and LPS groups were significantly worse than the control group, and especially the former had more obvious damages.(3) Prenatal stress—postnatal psychosocial-environmental changed model: only the LPS-stressed group was worse than the control group in the weight, sensorimotor, and spontaneous exploration and higher in anxiety than the control group. However, LPS-enriched group could alleviate anxiety in the black–white alley task.(4) The proteins levels: i) The different psychosocial-environmental models in young mice: compared with the young controls, the level of HDAC2 expression significantly increased in the old controls, but PSD95 and Syn significantly reduced. These changes exhibited age-related characteristics. Compared with the enriched and control groups, the stressed group had significantly increased HDAC2 and decreased Syn at 12 months old. At 18 months old, only the enriched group had significantly reduced HDAC2 and increased Syn and PSD95 compared with the stressed group. ii) Adverse environment during pregnancy—postpartum stress model: compared with the control group, the LPS and LPS-stressed groups had significantly reduced levels of Syn and PSD95, and marginal increased HDAC2 in the LPS-stressed group. iii) Prenatal stress—postnatal psychosocial-environmental changed model: the LPS-stressed group had significantly reduced PSD95, but marginally affected HDAC2 and Syn compared with the control group in offspring mice. Furthermore, according to the correlation analysis, the increased level of HDAC2 was significantly negative correlations with the abilities of learning and memory in the MWM. In contrast, the levels of PSD95 and Syn showed a positive correlation with these spatial abilities of learning and memory. SummaryMaternal inflammation and stress, with a synergistic effect, could worsen the changes of age-related behaviors and hippocampal neurobiological indicators. However, the enriched environment could alleviate these aging changes. In addition, epigenetic modifications and synaptic plasticity might participate in these changes.