Assessment of white matter disconnection and Ferroptosis in chronic kidney disease mouse

Motivation: Cognitive decline is common in chronic kidney disease (CKD), yet the mechanisms behind the CKD-related cognitive decline remain unknown. Goal(s): To explore the brain injury patterns and pathological mechanisms underlying CKD-related cognitive decline. Approach: We constructed whole-brain white matter connectome using diffusion MRI from CKD mouse, computed the measures of network topology, and further characterized pathological changes in the brain using staining, western blot, transcriptomics and flow cytometry techniques. Results: We found that the decreased rich club edge in the hippocampus was profound in CKD mouse with cognitive deterioration and the potential therapeutic mechanism of resveratrol in targeting ferroptosis. Impact: CKD-associated cognitive impairment is predominantly caused by the ferroptosis-induced dysconnectivity and destruction of the rich-club subnetwork, especially in the hippocampus. The ferroptosis-inhibitor-resveratrol may serve as the therapeutic method for improving cognitive function in CKD patients.