Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

Protective Effect of Environmental Enrichment on the Morphology of Neurons in the Motor Cortex of Diabetic and Stressed Rats

Background:The present study aimed to evaluate the effects of EE on the morphology of pyramidal neuron at the motor cortex of diabetic and stressed rats.Methods and materials:Male Wistar rats were grouped into Normal Control (NC), Vehicle Control (VC), Diabetes (D), Diabetes + Stress (D+S), Diabetes + Environmental Enrichment (D+EE) and Diabetes + Stress +Environmental Enrichment (D+S+EE) (n=8). Hyperglycemia was induced in Westar rats using streptozotocin (40mg/kg; ip). Blood sugar levels and body weight was measured at regular intervals to monitor the development of hyperglycemia. All experimental groups were housed in standard cages throughout the experiment. Rats in groups D+S and D+S+EE were transferred into space restrained cages for 6 hours daily. D+S+EE group were transferred into EE cages immediately after the space restrained session for subsequent 6 hours daily. On day 30, all rats were sacrificed and brains were harvested and prepared for rapid Golgi staining protocol. Dendritic branchings and dendriticintersections of the motor cortex neurons were quantitated using a camera lucida attached to Biolux research microscope. Data was analyzed using ANOVA with Bonferroni’s test.