Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND

Perioperative neurocognitive disorders (PND) are common complications observed in surgical patients, but there are no effective treatments and the detailed mechanisms remain largely unknown. In this study, transcriptome analysis was performed to investigate the hippocampal changes after surgery and underlying molecular mechanisms of PND. Tibial fracture surgery was performed in 3–4 months old C57BL/6J mice to mimic human orthopedic surgery. We demonstrated that memory consolidation of the hippocampal-dependent trace-fear conditioning task was significantly impaired. By using ELISA, a significant elevated IL-6 was observed both in circulating system and central nervous system and peaked at 6 h post-surgery, but transiently returned to baseline thereafter. Hippocampus were collected at 6 h post-surgery then processed for RNA-Seq. A total of 268 genes were screened differentially expressed between the Surgery and Control group, including 170 up-regulated genes and 98 down-regulated genes. By functional enrichment analysis of differently expressed genes, several KEGG pathways involved in inflammatory mediator regulation of TRP channels, neuroactive ligand-receptor interaction and cholinergic synapse were overrepresented. Quantitative real-time PCR confirmed 15 dysregulated genes of interest. These results provide a comprehensive insight into global gene expression changes during the acute presence of hippocampal inflammation and a better understanding on early stage of PND

WRKY33-PIF4 loop is required for the regulation of H₂O₂ homeostasis

The reactive oxygen species (ROS) are continuously produced and are essential for mediating the growth and development of plants. However too much accumulation of ROS can result in the oxidative damage to cells, especially under the adverse environmental conditions. Plants have evolved sophisticated strategies to regulate the homeostasis of H2O2. In this study, we generated transgenic Arabidopsis plants in the Ws ecotype (Ws) background in which WRKY33 is co-suppressed (csWRKY33/Ws). Compared with Ws, csWRKY33/Ws plants accumulate more H2O2. RNA-seq analysis indicated that in csWRKY33/Ws plants, expression of oxidative stress related genes such as ascorbate peroxidase 2 (APX2) is affected. Over-expression of APX2 can rescue the phenotype of csWRKY33/Ws, suggesting that the changes in the growth of csWRKY33/Ws is duo to the higher accumulation of H2O2. Analysis of the CHIP-seq data suggested that WRKY33 can directly regulate the expression of PIF4, vice versa. qPCR analysis also confirmed that the mutual regulation between WRKY33 and PIF4. Similar to that of csWRKY33/Ws, and the accumulation of H2O2 in pif4 also increased. Taken together, our results reveal a WRKY33-PIF4 regulatory loop that appears to play an important role in regulating the growth and development of seedlings by mediating H2O2 homeostasis