Maternal sleep deprivation disrupts glutamate metabolism in offspring rats

Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspring cognitive development,with a particular focus on alterations in glutamate metabolism.Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1,P7,P14,and P56)and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry.Metabolomic analysis revealed significant differences in various amino acids,including L-glutamate,L-phenylalanine,L-tyrosine,and L-tryptophan,which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA)demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development.KEGG pathway analysis revealed differential regulation of several pathways,including alanine,aspartate,and glutamate metabolism,glutathione metabolism,arginine biosynthesis,aminoacyl-tRNA biosynthesis,histidine metabolism,and taurine and hypotaurine metabolism,at different developmental stages.Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus_1,Ruminococcaceae_UCG-005,and Eubacterium_coprostanoligenes_group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway.Collectively,these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring,particularly impacting pathways linked to cognitive function.This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.

Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats

Maternal sleep deprivation(MSD)is a global public health problem that affects the physical and mental development of pregnant women and their newborns.The latest research suggests that sleep deprivation(SD)disrupts the gut microbiota,leading to neuroinflammation and psychological disturbances.However,it is unclear whether MSD affects the establishment of gut microbiota and neuroinflammation in the newborns.In the present study,MSD was performed on pregnant SpragueDawley rats in the third trimester of pregnancy(gestational days 15-21),after which intestinal contents and brain tissues were collected from offspring at different postnatal days(P1,P7,P14,and P56).Based on microbial profiling,microbial diversity and richness increased in pregnant rats subjected to MSD,as reflected by the significant increase in the phylum Firmicutes.In addition,microbial dysbiosis marked by abundant Firmicutes bacteria was observed in the MSD offspring.Furthermore,quantitative real-time polymerase chain reaction(q RT-PCR)and enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of proinflammatory cytokines interleukin 1β(IL-1β)and tumor necrosis factorα(TNF-α)were significantly higher in the MSD offspring at adulthood(P56)than in the control group.Through Spearman correlation analysis,IL-1βand TNF-αwere also shown to be positively correlated with Ruminococcus_1 and Ruminococcaceae_UCG-005 at P56,which may determine the microbiota-host interactions in MSDrelated neuroinflammation.Collectively,these results indicate that MSD changes maternal gut microbiota and affects the establishment of neonatal gut microbiota,leading to neuroinflammation in MSD offspring.Therefore,understanding the role of gut microbiota during physiological development may provide potential interventions for cognitive dysfunction in MSD-impacted offspring.