Declarative and Procedural Memory Dependent Behavioural Function in a Transgenic Rat Model of Huntington’s Disease: A Novel Paradigm
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1
University Hospital Freiburg, Sterotactic and Functional Neurosurgery, Germany
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2
University Hospital Freiburg, Nuclear Medicine, Germany
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3
Forschungszentrum Jülich, Institute of Neuroscience and Medicine, Germany
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4
Friedrich-Alexander-University Nürnberg / Erlangen, Section for Experimental Therapy, Germany
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5
Université de Strasbourg, Faculté de Psychologie, France
Huntington’s Disease (HD) is a debilitating disease impacting on the individual’s motor, affective and cognitive function and there are no cures or effective therapies today. The predominant pathological signature of the Huntington’s disease is the early and progressive loss of GABAergic medium spiny projection neurones from within the striatum. However, anatomical and metabolic changes in other regions have been described in asymptomatic, pre-clinical stages of the disease. Deficits in the fronto-striatal loop result in impairment in new learning and cognitive rigidity. These detriments can be offset by compensatory increases in hippocampal based memory systems. We chose to use a transgenic rat model of HD to examine memory capacity and whether this higher order function declines in any way comparable to the changes in declarative and procedural memory observed in HD patients.
40 transgenic rats (tgHD) obtained from three pooled litters, comprised of all genotypes, were used in this study. Behavioural tests were conducted at 6-8 months and again at 12-14 months of age. Each behavioural battery of tests consisted of motoric (rotorod, grip strength) and cognitive (elevated plus maze, Morris water maze, double-H maze) elements. Additionally, 13 of the tgHD rats were examined by PET at 7 and 14 months of age. A dopamine D2-receptor radioligand was employed to examine anatomical and functional data.
Overall, transgenic animals demonstrated poorer performance in motoric behavioural tests, as compared to wildtype litter mates. Little or no differences were observed during the first testing session, whereas slight to modest deficiencies were found when the animals were tested at 12-14 months, consistent with reported observations. In contrast, transgenic animals displayed inferior results in cognitive tests already at 6-8 months, which were more pronounced in the second testing session. Transgenic animals were able to learn the tasks, yet showed poor retention over time. They were able to relearn the tasks, albeit at a slower rate than wildtypes. This was most exacerbated in homozygote females. This population also spent larger amounts of time outside of the closed arms in the elevated plus maze, displaying a disturbed sense of anxiety. This likely contributed to the learning / memory deficits observed. PET examination revealed minimal changes (~2-3 %) groups homozygotes and wildtype animals at both time points tested. However, one individual showed marked receptor loss (~50 %) at 14 months. Finally, immunohistochemical analysis is underway, which will be used to correlate cellular pathology with the behavioural findings. The significance of these results in relation to disease progression will be discussed.
Keywords:
animal model,
Huntington's disease,
Long-term memory,
transgenic
Conference:
BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.
Presentation Type:
Poster
Topic:
brain disease, network dysfunction and intervention (please use "brain disease, network dysfunction and intervention" as keyword)
Citation:
Kirch
R,
Deininger
F,
Gehrig
S,
Meyer
P,
Klein
S,
Von Horsten
S,
Nikkhah
G,
Cassel
J and
Döbrössy
M
(2011). Declarative and Procedural Memory Dependent Behavioural Function in a Transgenic Rat Model of Huntington’s Disease: A Novel Paradigm.
Front. Comput. Neurosci.
Conference Abstract:
BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011.
doi: 10.3389/conf.fncom.2011.53.00199
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Received:
19 Aug 2011;
Published Online:
04 Oct 2011.
*
Correspondence:
Dr. Robert Kirch, University Hospital Freiburg, Sterotactic and Functional Neurosurgery, Freiburg, 79106, Germany, robert.kirch@uniklinik-freiburg.de