title: Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for huntington disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuropharmacology, EVOTEC AG, Hamburg, Germany. yah-se.abada@evotec.com
authors.forename: Yah-Se K
authors.initials: YS
authors.lastname: Abada
authors.forename: Huu Phuc
authors.initials: HP
authors.lastname: Nguyen
authors.forename: Rudy
authors.initials: R
authors.lastname: Schreiber
authors.forename: Bart
authors.initials: B
authors.lastname: Ellenbroek
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005684:Gait / Q000502:physiology; D005838:Genotype; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000502:physiology*; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D021641:Recognition, Psychology / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D055139:Sensory Gating / Q000235:genetics / Q000502:physiology*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins