Enriched environment for offspring improves learning and memory impairments induced by sevoflurane exposure during the second trimester of pregnancy

Studies in animals indicate that sevoflurane exposure in the second trimester of pregnancy has harmful effects on the learning and memory of offspring.Whether an enriched environment can reverse the damage of sevoflurane exposure in the second trimester of pregnancy on the learning and memory of rat offspring remains unclear.In this study,rats at 14 days of pregnancy were exposed to 3.5%sevoflurane for 2 hours and their offspring were treated with an enriched environment for 20 successive days.We found that the enriched environment for offspring increased nestin and Ki67 levels in hippocampal tissue,increased hippocampal neurogenesis,inhibited glycogen synthase kinase 3βactivity,and increased the expression of cell proliferation-relatedβ-catenin and apoptosis-related Bcl-2,indicating that an enriched environment reduces sevoflurane-induced damage by increasing the proliferation of stem cells in the hippocampus.These findings suggest that an enriched environment can reverse the effects of sevoflurane inhaled by rats during the second trimester of pregnancy on learning and memory of offspring.This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018PS07K)on January 2,2018.

Effects of mild intrauterine hypoperfusion in the second trimester on memory and learning function in rat offspring

Mild intrauterine hypoperfusion(MIUH)is a serious pathological event that affects the growth and development of fetuses and offspring.MIUH can lead to growth restriction,low birth weight,neurodevelopmental disorders,and other adverse clinical outcomes.To study the effects of MIUH on learning and memory function in offspring,a model of MIUH was established by placing a coil(length 2.5 mm,diameter 0.24 mm)on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy(day 17).Next,120 mg/kg lithium chloride(the MIUH+Li group)or normal saline(the MIUH group)was injected intraperitoneally into these rats.In addition,120 mg/kg lithium chloride(the Li group)or normal saline(the SHAM group)was injected intraperitoneally into pregnant rats without coil placement.The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth.In the MIUH group,the escape latency and journey length before reaching the platform were both increased,and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group.Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67(both cell-proliferation-related proteins)expression was significantly downregulated in the MIUH group compared with the SHAM group.Furthermore,western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats,and revealed that glycogen synthase kinase 3β(GSK3β)expression was upregulated andβ-catenin expression was downregulated in the MIUH group compared with the SHAM group.In addition,compared with the MIUH group,the expression levels of p-GSK3βandβ-catenin were upregulated in the MIUH+Li group.These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3βsignaling pathway.The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018 PS07 K)in June 2018.