The effects of chronic kidney disease and cardiometabolic risk factors on neurocognitive dysfunction in mice
Embargo Date
2028-02-18
OA Version
Citation
Abstract
Chronic kidney disease (CKD) has been known to increase the risk of developing cognitive impairment in both clinic and research settings. The mechanism by which this occurs is in the nascent stages of discovery largely because very little has been done to understand the cross talk between the kidney and the brain. Interest in elucidating the kidney-brain axis is growing; however, there is an absence of adequate models that fully capture the effects of CKD on cognitive dysfunction. In this study we used mouse models for CKD, obesity, and a combined model for chronic kidney disease and obesity to encapsulate cardiovascular kidney metabolic syndrome (CKM), a more comprehensive representation of CKD, to assess for neurocognitive dysfunction in mice. We assessed the functional implications through open field and novel object recognition testing, while examining the structural defects in the brain using immunofluorescent staining of astrocytes. Behavioral analysis confirmed that CKD induces neurocognitive decline, obesity elicits no change in function, and CKM offers an improvement compared to just CKD alone. Analysis of astrocytes show that individually CKD and obesity decrease GFAP expression. For the first time, in this work we characterize the effects of CKM on neurocognitive decline in mice.
Description
2025