Relevance of the hippocampal endoplasmic reticulum stress response in a mouse model of chronic kidney disease.

It has been shown that the incidence of cognitive impairment increases with the severity of chronic kidney disease (CKD). A previous study has demonstrated that hippocampal oxidative stress contributes to cognitive dysfunction in CKD model mice. Endoplasmic reticulum (ER) stress is thought to contribute significantly to neuronal dysfunction, but its role in the hippocampal dysfunction seen in CKD still remains unclear. The present study examined whether the ER stress response as well as oxidative stress was activated in the hippocampus of CKD model mice. Western blotting revealed that the expression level of 4-hydroxy-2-nonenal (HNE)-protein adducts, a marker of oxidative stress, was increased in the hippocampus 8 weeks after 5/6 nephrectomy. In these mice, the expression level of glucose-regulated protein 78 (GRP78), a typical ER stress marker, also showed a pronounced increase in the hippocampus. Correlation analyses showed that the levels of these two marker proteins in the hippocampus are positively correlated with the serum concentrations of BUN and creatinine. These results suggest that ER stress as well as oxidative stress are induced in the hippocampus of CKD mice and that the levels of these stress markers in the hippocampus are correlated with the renal impairment caused by CKD.