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

Autor: Huu Phuc Nguyen, Yah-se K. Abada, Bart A. Ellenbroek, Rudy Schreiber
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
NEUROPATHOLOGICAL FEATURES
HD
Reflex
Startle
Startle response
SYMPTOMS
Huntingtin
lcsh:Medicine
MUTANT HUNTINGTIN
0302 clinical medicine
YAC128 MOUSE MODEL
lcsh:Science
Gait
Prepulse inhibition
Huntingtin Protein
0303 health sciences
Multidisciplinary
Behavior
Animal
medicine.diagnostic_test
Neuropsychology
Sensory Gating
3. Good health
Motor coordination
Huntington Disease
Rats
Transgenic
Research Article
ACOUSTIC STARTLE
Genotype
GENE CARRIERS
Nerve Tissue Proteins
Motor Activity
Biology
PREPULSE INHIBITION
03 medical and health sciences
Memory
medicine
Animals
Humans
030304 developmental biology
Recognition memory
lcsh:R
Recognition
Psychology
Rats
Disease Models
Animal
MICE
COGNITIVE DEFICITS
Rotarod Performance Test
Mutation
lcsh:Q
Cognition Disorders
Hypoactivity
Neuroscience
030217 neurology & neurosurgery
Zdroj: PLoS ONE, Vol 8, Iss 7, p e68584 (2013)
PLoS ONE, 8(7):e68584. PUBLIC LIBRARY SCIENCE
PLoS ONE
ISSN: 1932-6203
Popis: Rationale: 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.Objectives: The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats.Materials and 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.Conclusion: 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.
Databáze: OpenAIRE
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