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C08 Set-shifting Deficits In The Pre-symptomatic Bachd Transgenic Rat Model Of Huntington’s Disease
  1. MV Sosti1,2,3,
  2. S Martínez-Horta1,2,
  3. J Pérez Pérez1,2,
  4. F Arenas1,2,3,
  5. J Kulisevsky1,2,3,4
  1. 1Movement Disorders Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Mas Casanoves 90, 08025, Barcelona, Spain
  2. 2Biomedical Research Institute Sant Pau (IIB-Sant Pau), Mas Casanoves 90, 08025, Barcelona, Spain
  3. 3Neuropsicopharmacology Lab, Building 19 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  4. 4Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain

Abstract

Background Cognitive deterioration mainly characterised as frontal-executive deficits is intrinsic to Huntington’s disease (HD) and identifiable years before motor-based clinical onset. Although behavioural, cognitive and neuropathological changes have been described in a novel BACHD rat model, little is known about the presence of measurable frontal-executive alterations in pre-symptomatic animals.

Objectives We aimed to investigate set-shifting performance in a longitudinal approach along the course of the disease. Here we present the cross-sectional results.

Methods Wild type (n = 20) and transgenic (n = 20) male BACHD rats were tested at 8 weeks-aged. Motor function (locomotor activity) was assessed through a photoelectric actimeter.Set-shifting performance was evaluated through the attentional set-shifting paradigm described by Birrell and Brown. Reversal learning and acquisition/shifting on intra-dimensional (IDS) and extra-dimensional (EDS) stages were measured. The total number of trials done to achieve six consecutive correct responses was used as performance measure. Data were subjected to unpaired t-test and repeated measures ANOVA.

Results No alterations in clasping behaviour were found in BACHD rats. Compared to wild-type, BACHD rats appeared significantly slower (964.8 ± 58.6 vs 1300 ± 73.6; p = 0.002). No differences were found regarding reversal learning and IDS. Conversely, BACHD rats made a significantly higher number of EDS errors than wild-type (14.6 ± 0.6 vs 12 ± 0.4; p < 0.001).

Conclusions A well differentiated pattern of more impaired set-shifting performance is measurable in transgenic animals and distinguishes BACHD from wild-type rats during the pre-symptomatic stage. Despite longitudinal data are needed, set-shifting performance apparels as a potentially useful biomarker to track the progression of the disease in the BACHD rat model.

KeyWords
  • Huntington’s disease
  • BACHD
  • set-shifting

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