An enriched environment improves maternal sleep deprivation- induced cognitive deficits via hippocampal histone acetylation

Growing evidence clearly demonstrates that maternal rodents exposure to sleep deprivation during late pregnancy impairs learning and memory in their offspring. Epigenetic mechanisms, particularly histone acetylation, are known to be involved in synaptic plasticity, learning, and memory. We investigated whether cognitive decline induced by sleep deprivation during late-pregnancy is associated with histone acetylation dysfunction and whether this effect could be reversed by an enriched environment (EE). In the present study, pregnant CD-1 mice were exposed to sleep deprivation during the third trimester of pregnancy. After weaning, all offspring were randomly assigned to two subgroups in either a standard environment or an EE. When offspring were three months old, the Morris water maze was used to evaluate hippocampal-dependent learning and memory ability. Molecular biological techniques, including western blot and real-time fluorescence quantitative polymerase chain reaction, were used to examine histone acetylation pathway and synaptic plasticity markers in the hippocampus of offspring. Our results showed that the following were all reversed by EE treatment: maternal sleep deprivation (MSD)-induced cognitive deficits including spatial learning and memory; histone acetylation dysfunction including increased histone deacetylase 2 (HDAC2) and decreased histone acetyltransferase (CBP), and the acetylation levels of H3K9 and H4K12; synaptic plasticity dysfunction including decreased brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD-95). The results suggested that MSD could damage learning ability and memory in offspring via the histone acetylation pathway. This effect could be reversed by EE treatment.