Original Research ARTICLE
McGill transgenic rat model of Alzheimer's disease displays cognitive and non-cognitive impairments and altered circadian clock function
- 1Department of Neurophysiology of Memory, Institute of Physiology (ASCR), Czechia
- 2Department of Neurohumoral Regulations, Institute of Physiology (ASCR), Czechia
- 3National Institute of Mental Health (Czechia), Czechia
The McGill-R-Thy1-APP transgenic rat is an animal model of the familial form of Alzheimer’s disease (AD), mirroring many neuropathological hallmarks of the disease and gradual deterioration of cognitive functions. In this study, we describe thorough characterization of the model in several domains.
On the behavioral level, we report normal locomotor activity in spontaneous exploration, but problems with balance or gait coordination, increased anxiety and severely impaired spatial cognition in 4 - 7 months old animals. The profile of social behavior and ultrasonic communication is altered in the McGill rats, without a general social withdrawal.
McGill rats also exhibit changes in circadian profile, with shorter free-running period and increased total activity during subjective night, without signs of sleep disturbances during the inactive phase. Expression of circadian clock gene Bmal1 was found to be increased in the parietal cortex and cerebellum, while Nr1d1 expression was not changed. The clock-controlled gene Prok2 expression was found to be elevated in the parietal cortex and hippocampus, which might contribute to the observed changes in circadian phenotype.
We conclude that the AD-like phenotype in the rat model is not restricted to cognitive domain, but also includes gait problems, changes in emotionality, social behavior and circadian profiles, paralleling the spectrum of symptoms observed in human patients and enabling development of new therapeutic approaches targeting not only memory decline but also other symptoms decreasing the quality of life of the patients.
Keywords: Alzheimer´s disease, transgenic, rat, Cognition, Social Behavior, Circadian system, amyloid precursor protein
Received: 20 Mar 2018;
Accepted: 31 Jul 2018.
Edited by:Nibaldo C. Inestrosa, Pontificia Universidad Católica de Chile, Chile
Reviewed by:Marina Bentivoglio, Università degli Studi di Verona, Italy
Paul Lucassen, University of Amsterdam, Netherlands
Copyright: © 2018 Petrásek, Vojtechova, Lobellová, Popelíková, Janíková, Brožka, Houdek, Sládek, Sumová, Kristofikova, Valeš and Stuchlik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Tomáš Petrásek, Institute of Physiology (ASCR), Department of Neurophysiology of Memory, Videnska 1083, Prague, 142 20, Czechia, firstname.lastname@example.org
Dr. Ales Stuchlik, PHD.., Institute of Physiology (ASCR), Department of Neurophysiology of Memory, Videnska 1083, Prague, 142 20, Czechia, email@example.com