B010 Behavioural changes and opisthotonus-like movements in the F344tgHD transgenic rat model of Huntington’s disease
Year: 2024
Type: conference-abstract
Abstract: Background A range of genetic mouse models are available to study Huntington’s disease (HD), although most have CAG repeats well in excess of that seen in adult HD and a relatively aggressive disease progression. The transgenic F344tgHD rat expresses a 51 CAG repeat fragment and exhibits a slow progressive phenotype that may be more typical of human adult-onset HD. Aims We sought to characterise motor and cognitive changes in the F344tgHD transgenic rat model, with a focus on understanding the manifestation of opisthotonus-like movements. Methods Wild type (WT), low mHTT expressing (mHTT low) and high mHTT expressing (mHTT high) rats were assessed for motor and cognitive deficits. Opisthotonos-like movements were quantified longitudinally, with pharmacological modulation at 5 and 18 months of age. The 5-choice serial reaction time task (5CSRTT), probing cognitive function, was undertaken at 12 months of age. Results Opisthotonos-like movements were observed in mHTT high rats as early as 2 months of age and persisted throughout the animal’s lifetime. Pharmacological challenge indicated these to be dopamine-mediated-behaviours. In the 5CSRTT, mHTT high rats performed significantly fewer total trials, were significantly less impulsive and omitted more responses compared to WT rats. Conclusion These data suggest that alterations of the dopamine system may be instrumental in the manifestation of opisthotonos-like movements in the F344tgHD rats. F344tgHD rats also demonstrate motivational deficits. This data will contribute to a larger longitudinal analysis of F344tgHD rat behaviour that aims to provide a more slowly progressive HD model for therapeutic testing, combined with the advantages of the larger rat brain.
Institution: Cardiff University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402373704