Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for huntington disease

• Published in: PloS one Vol. 8; no. 7; p. e68584
• Main Authors: Abada, Yah-Se K, Nguyen, Huu Phuc, Schreiber, Rudy, Ellenbroek, Bart
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.07.2013; Public Library of Science (PLoS)
• Subjects: Abnormalities; Acoustic startle response; Acoustics; Age; Animal cognition; Animals; Automation; Behavior, Animal - physiology; Cognition Disorders - genetics; Cognition Disorders - metabolism; Cognition Disorders - physiopathology; Cognitive ability; Disease Models, Animal; Drug discovery; Gait; Gait - physiology; Gating; Genetic engineering; Genotype; High definition television; Humans; Huntingtin; Huntingtin Protein; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - physiopathology; Huntington's disease; Huntingtons disease; Hyperactivity; Locomotor activity; Male; Memory; Memory - physiology; Motor Activity - genetics; Motor Activity - physiology; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuropathology; Object recognition; Pattern recognition; Phenotyping; Polyglutamine; Psychiatry; Rats; Rats, Transgenic; Recognition (Psychology) - physiology; Reflex, Startle - physiology; Rodents; Rotarod Performance Test - methods; Sensorimotor gating; Sensory Gating - genetics; Sensory Gating - physiology; Startle response; Transgenic; Trinucleotide repeats
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068584

Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes.