Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice.

AIMS: This study explored whether surgical stress-induced glucocorticoid receptor (GR) phosphorylation is related to postoperative cognitive dysfunction (POCD) in aged individuals. Inhibition of GR activation could be an effective treatment for POCD. METHODS: A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6 months old. Animals in control group were treated in identical manners except for laparotomy. Cognitive function was evaluated by Morris water maze and elevated plus maze. Western blot and Elisa assay were used to detect related molecules. Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation. RESULTS: The cognitive function was impaired, and brain-derived neurotrophic factor (BDNF) was found reduced in aged POCD group. GR translocation into nucleus and elevated GR phosphorylation were found in prefrontal cortex of aged POCD mice. Cyclin-dependent Kinase 5 (CDK5), kinase for GR phosphorylation also elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of BDNF and cognitive dysfunction in aged mice were both rescued. CONCLUSION: These results presented a mechanism that surgical stress-induced GR phosphorylation contributes to POCD in aged individuals. Inhibition of GR activation and phosphorylation might be a potential treatment target of POCD.

[Analysis of gene expression profile of peripheral ganglia in early stage type â ¡ diabetic rats].

Diabetic neuropathy (DN) is defined as the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes. The aim of this study is to screen differentially expressed genes in peripheral ganglia in early stage type Ⅱ experimental diabetic rats. We compared gene expression profiles of peripheral ganglia in type Ⅱ diabetic and nondiabetic rats based on Illumina® Sentrix® BeadChip arrays. The results showed that 158 out of a total of 12 604 known genes were significantly differentially expressed, including 87 up-regulated and 71 down-regulated genes, in diabetic rats compared with those in the nondiabetic rats. It is noted that some up-regulated genes are involved in the biological processes of neuronal cytoskeleton and motor proteins. In contrast, the down-regulated genes are associated with the response to virus\biotic stimulus\ other organism in diabetic rats. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the most significant pathway enriched in the changed gene set is metabolism (P < 0.001). These results indicated that metabolic changes in peripheral ganglia of diabetic rats could be induced by hyperglycemia. Hyperglycemia could change the expression of genes involved in neuronal cytoskeleton and motor proteins through immune inflammatory response, and then impair the structure and function of the peripheral ganglia.