Impact of unilateral ureteral obstruction on cognition and neurodegeneration
Autor: | Susan Yung, Jia Yan Tan, Joyce Man-Fong Lee, Raymond Chuen-Chung Chang, Yuen Shan Ho, Chi Fai Lau, Krit Lee |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Urology Hyperphosphorylation urologic and male genital diseases Systemic inflammation Kidney Transforming Growth Factor beta1 03 medical and health sciences Mice 0302 clinical medicine Cognition medicine Hippocampus (mythology) Animals Cognitive Dysfunction Maze Learning biology business.industry Tumor Necrosis Factor-alpha General Neuroscience Neurodegeneration Brain Neurodegenerative Diseases Recognition Psychology medicine.disease Disease Models Animal Oxidative Stress 030104 developmental biology Synaptophysin biology.protein Cytokines medicine.symptom business Complication 030217 neurology & neurosurgery Biomarkers Kidney disease Ureteral Obstruction |
Zdroj: | Brain research bulletin. 169 |
ISSN: | 1873-2747 |
Popis: | 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. |
Databáze: | OpenAIRE |
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