Validation of behavioral phenotypes in the BACHD rat model

Arianna Novati; Giuseppe Manfré; Stefanie Flunkert; Johanneke E Van der Harst; Judith R Homberg; Robert Wronski; Huu Phuc Nguyen

doi:10.1016/j.bbr.2020.112783

Validation of behavioral phenotypes in the BACHD rat model

Behav Brain Res. 2020 Sep 1:393:112783. doi: 10.1016/j.bbr.2020.112783. Epub 2020 Jun 20.

Authors

Arianna Novati¹, Giuseppe Manfré², Stefanie Flunkert³, Johanneke E Van der Harst⁴, Judith R Homberg⁵, Robert Wronski³, Huu Phuc Nguyen⁶

Affiliations

¹ 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.
² 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.
³ QPS Austria GmbH, Neuropharmacology, Parkring 12, 8074, Grambach, Austria.
⁴ 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.
⁵ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Postbus 9104, 6500 HE, Nijmegen, the Netherlands.
⁶ 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.

PMID: 32574646
DOI: 10.1016/j.bbr.2020.112783

Abstract

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.

Keywords: BACHD rats; Behavioral phenotype validation; Behavioral phenotyping.

Publication types

Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Animals
Avoidance Learning
Behavior, Animal*
Disease Models, Animal*
Huntington Disease / psychology*
Male
Maze Learning
Phenotype
Rats
Rats, Sprague-Dawley
Rotarod Performance Test