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Profiles of motor and cognitive impairment in the transgenic rat model of Huntington's disease

Fielding, Steven A., Brooks, Simon Philip ORCID:, Klein, Alexander, Bayram-Weston, Zubeyde, Jones, Lesley ORCID: and Dunnett, Stephen Bruce ORCID: 2012. Profiles of motor and cognitive impairment in the transgenic rat model of Huntington's disease. Brain Research Bulletin 88 (2-3) , pp. 223-236. 10.1016/j.brainresbull.2011.09.011

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The transgenic Huntington's disease (tgHD) rat strain provides a well regarded transgenic animal model of Huntington's disease, offering the prospect for a more detailed functional analysis in rats, along with neurological and therapeutic interventions, than is possible in the more widely available mouse models. In the present experiments, we compare the performance of heterozygous and homozygous tgHD rats against wildtype littermates on a range of motor and cognitive assessments in five separate cohorts of rats between 8 and 22months of age. Male but not female heterozygous tgHD rats exhibit modest motor deficits in rotarod and staircase reaching tests, whereas most cognitive tests (including object recognition, exploration of novelty, delayed alternation, choice reaction time, and serial implicit learning tasks) revealed at best small or inconsistent deficits, in homozygous as well as heterozygous animals, up to 22months of age. Thus, although we have observed modest but clear-cut deficits in motor phenotype, with a sex difference in line with previous reports, we have not established a robust cognitive impairment in this strain on a range of tasks sensitive to frontostriatal function, as required for testing novel (symptomatic, protective or reparative) therapeutics in a robust, valid, animal model of human Huntington's disease.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: tgHD rats; Phenotype; Frontostriatal function; Motor tests; Cognitive tests; Huntington inclusions
Publisher: Elsevier
ISSN: 0361-9230
Funders: Medical Research Council of the UK, CHDI Inc., EU Framework 7 NeuroStemCell programme
Last Modified: 19 Oct 2022 09:06

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