Impact of unilateral ureteral obstruction on cognition and neurodegeneration

Yuen Shan Ho, Chi Fai Lau, Krit Lee, Jia Yan Tan, Joyce Lee, Susan Yung, Raymond Chuen Chung Chang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Introduction: Cognitive impairment is a common complication in chronic kidney disease (CKD) patients. Currently, limited types of animal models are available for studying cognitive impairment in CKD. We used unilateral ureteral obstruction (UUO) in mice as an animal model to study the cognitive changes and related pathology under prolonged renal impairment Methods: UUO was performed in 8-week-old male C57BL/6 N mice with double-ligation of their left ureter. A sham group was subjected to the same experimental procedure without ureteral obstruction. Cognitive and behavioral tests were performed to examine potential changes in cognition and behavior at 2, 4 and 12 weeks after surgery. Sera were collected, and kidneys and brains were harvested for the detection of systemic inflammation markers and neurodegenerative changes. Results: These mice displayed weak performance in the novel object recognition test, Y-maze test, and puzzle box test compared to the sham group. Reductions in synaptic proteins such as synapsin-1, synaptophysin, synaptotagmin, PSD95, NMDAR2B and AMPAR were confirmed by western blot analysis. Histological examination revealed elevated levels of Nrf2 and 8-hydroxyguanosine, and hyperphosphorylation of tau in the hippocampus. UUO mice also had increased levels of C-reactive protein (CRP) and TNF-α. Conclusions: We characterized the cognitive and neuropathological changes in UUO mice. The results show that this mouse model can be used to further study cognitive changes related to chronic renal impairment.

Original languageEnglish
Pages (from-to)112-127
Number of pages16
JournalBrain Research Bulletin
Volume169
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Cognitive impairment
  • Inflammation
  • Oxidative stress
  • Renal impairment
  • Synapse
  • Tau phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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