Validation of behavioral phenotypes in the BACHD rat model.

Autor: Novati A; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstrasse7, 72076, Tübingen, Germany; Centre for Rare Diseases, University of Tübingen, Calwerstrasse7, 72076, Tübingen, Germany; QPS Austria GmbH, Neuropharmacology, Parkring 12, 8074, Grambach, Austria; Department of Human Genetics, Ruhr University Bochum, Universitätsstraße 150, 44801, Bochum, Germany., Manfré G; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstrasse7, 72076, Tübingen, Germany; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Postbus 9104, 6500 HE, Nijmegen, the Netherlands; Noldus Information Technology BV, Nieuwe Kanaal 5, 6709 PA, Wageningen, the Netherlands., Flunkert S; QPS Austria GmbH, Neuropharmacology, Parkring 12, 8074, Grambach, Austria., Van der Harst JE; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Postbus 9104, 6500 HE, Nijmegen, the Netherlands; Noldus Information Technology BV, Nieuwe Kanaal 5, 6709 PA, Wageningen, the Netherlands., Homberg JR; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Postbus 9104, 6500 HE, Nijmegen, the Netherlands., Wronski R; QPS Austria GmbH, Neuropharmacology, Parkring 12, 8074, Grambach, Austria., Nguyen HP; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstrasse7, 72076, Tübingen, Germany; Centre for Rare Diseases, University of Tübingen, Calwerstrasse7, 72076, Tübingen, Germany; Department of Human Genetics, Ruhr University Bochum, Universitätsstraße 150, 44801, Bochum, Germany. Electronic address: huu.nguyen-r7w@ruhr-uni-bochum.de.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2020 Sep 01; Vol. 393, pp. 112783. Date of Electronic Publication: 2020 Jun 20.
DOI: 10.1016/j.bbr.2020.112783
Abstrakt: Huntington disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion in the HTT gene. Various HD animal models have been generated to mimic the motor, cognitive and neuropsychiatric disturbances that affect HD patients. Reproducing disease phenotypes within these models is essential to identify reliable readouts for therapy studies. We validated behavioral phenotypes shown earlier by other research groups in the BACHD rat model, using both previously applied and novel tests for motor, cognitive and anxiety-like behaviors. We first confirmed known BACHD rats' phenotypes in rotarod, open field (OF) and elevated plus maze (EPM) tests. We then assessed the reproducibility of key phenotypes in the model using new tests: cliff hanging, passive avoidance (PA), Morris water maze (MWM), light dark box and light spot tests. We confirmed impaired motor coordination in the rotarod test and reduced activity in the OF. In line with earlier results in BACHD rats using different tests, we showed impaired reversal learning in MWM and decreased anxiety-like behavior with the light spot test supporting the validity of BACHD rats as a model of HD. Results in the EPM, light dark box, cliff hanging and PA tests did not confirm earlier findings. This may depend on phenotype inconsistencies or rather be related to differences in environmental variables, test typology, experimental settings, animal age and chosen behavioral parameters.
Competing Interests: Declaration of Competing Interest The authors declare that there are not competing financial interests.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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