Articles

Article

Original Article

Exp Neurobiol 2018; 27(4): 277-286

Published online August 30, 2018

https://doi.org/10.5607/en.2018.27.4.277

© The Korean Society for Brain and Neural Sciences

Assessment of Cognitive Impairment in a Mouse Model of High-Fat Diet-Induced Metabolic Stress with Touchscreen-Based Automated Battery System

Saeram Lee1,2,†, Jong Youl Kim1,†, Eosu Kim2,3, KyoungYul Seo4, Youn Jae Kang1,2, Jae Young Kim1, Chul-Hoon Kim2,5, Ho Taek Song6, Lisa M. Saksida7,8,9, and Jong Eun Lee1,2*

1Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea.

2BK21 PLUS Project for Medical Science, and Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea.

3Department of Psychiatry, Yonsei University College of Medicine, Seoul 03722, Korea.

4Department of Ophthalmology and The Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea.

5Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea.

6Department of Radiology, Yonsei University College of Medicine, Seoul 03722, Korea.

7Department of Psychology and MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.

8Canada Research Chair in Translational Cognitive Neuroscience, University of Western Ontario, London, ON N6G 2VA, Canada.

9Department of Pharmacology & Physiology, University of Western Ontario, London, ON N6G 2VA, Canada.

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2228-1646, FAX: 82-2-365-0700
e-mail: jelee@yuhs.ac
These authors contributed equally to this work.

Received: July 10, 2018; Revised: August 3, 2018; Accepted: August 6, 2018

Obesity-related metabolic disorders can affect not only systemic health but also brain function. Recent studies have elucidated that amyloid beta deposition cannot satisfactorily explain the development of Alzheimer's disease (AD) and that dysregulation of glucose metabolism is a critical factor for the sporadic onset of non-genetic AD. Identifying the pathophysiology of AD due to changes in brain metabolism is crucial; however, it is limited in measuring changes in brain cognitive function due to metabolic changes in animal models. The touchscreen-based automated battery system, which is more accurate and less invasive than conventional behavioral test tools, is used to assess the cognition of mice with dysregulated metabolism. This system was introduced in humans to evaluate cognitive function and was recently back-translated in monkeys and rodents. We used outbred ICR mice fed on high-fat diet (HFD) and performed the paired associates learning (PAL) test to detect their visual memory and new learning ability loss as well as to assess memory impairment. The behavioral performance of the HFD mice was weaker than that of normal mice in the training but was not significantly associated with motivation. In the PAL test, the average number of trials completed and proportion of correct touches was significantly lower in HFD mice than in normal diet-fed mice. Our results reveal that HFD-induced metabolic dysregulation has detrimental effects on operant learning according to the percentage of correct responses in PAL. These findings establish that HFD-induced metabolic stress may have an effect in accelerating AD-like pathogenesis.

Graphical Abstract


Keywords: Metabolic disorders, High-fat diet, Cognitive impairment, Paired Associates Learning test, Alzheimer's disease