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Published on: February 2, 2021
Animal models to study cognitive impairment of chronic kidney disease
Pedro H Imenez Silva1,2, Marion Pepin3,4, Andreja Figurek5
1Institute of Physiology, University of Zurich, Zurich, Switzerland.
Abstract:
Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives, and society. However, the underlying pathomechanisms are poorly understood, and current therapies mostly aim at supporting patients in their daily lives. This illustrates the urgent need to elucidate the pathogenesis and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modeling of cognitive disorders in CKD. We discuss the use of mice, rats, and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving the therapy of people with CKD and MCI.
Insights
Mild cognitive impairment (MCI) is common in chronic kidney disease (CKD). This study outlines criteria for preclinical models to understand MCI in CKD and accelerate new therapies.
Area of Science:
- Nephrology
- Neurology
- Translational Medicine
Background:
- Mild cognitive impairment (MCI) is prevalent in chronic kidney disease (CKD), increasing with kidney function decline.
- MCI involves cognitive decline beyond age/education norms, impacting daily living minimally.
- Pathomechanisms of MCI in CKD are unclear, necessitating research into pathogenesis and therapeutic targets.
Purpose of the Study:
- To establish criteria for experimental modeling of cognitive disorders in CKD.
- To facilitate preclinical research for improved therapies for CKD patients with MCI.
- To accelerate the development of novel therapeutic strategies.
Main Methods:
- Discussion of criteria for preclinical modeling of cognitive disorders in CKD.
- Evaluation of mice, rats, and zebrafish as suitable model systems.
- Presentation of techniques for assessing kidney function and cognitive impairment in models.
Main Results:
- The study provides a framework for developing and validating preclinical models of MCI in CKD.
- It highlights the utility of various animal models for studying the interplay between kidney function and cognition.
- Key assessment techniques for kidney function and cognitive deficits are presented.
Conclusions:
- Standardized preclinical models are crucial for understanding MCI pathogenesis in CKD.
- Research in animal models can identify novel therapeutic targets and accelerate clinical translation.
- This work aims to overcome research hurdles and improve therapeutic outcomes for CKD-associated MCI.
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