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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00250

McGill transgenic rat model of Alzheimer's disease displays cognitive and non-cognitive impairments and altered circadian clock function

 Tomáš Petrásek1, 2, 3*,  Iveta Vojtechova1, 2, 3,  Veronika Lobellová1, 2,  Anna Popelíková1, 2, Martina Janíková1, 2,  Hana Brožka1, 2, Pavel Houdek2, Martin Sládek2,  Alena Sumová2,  Zdenka Kristofikova3, Karel Valeš1, 2, 3 and  Ales Stuchlik1, 2*
  • 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.

* Correspondence:
Dr. Tomáš Petrásek, Institute of Physiology (ASCR), Department of Neurophysiology of Memory, Videnska 1083, Prague, 142 20, Czechia, disworlds@gmail.com
Dr. Ales Stuchlik, PHD.., Institute of Physiology (ASCR), Department of Neurophysiology of Memory, Videnska 1083, Prague, 142 20, Czechia, ales.stuchlik@fgu.cas.cz