Title: Poster session: Impaired hippocampus-dependent learning and synaptic plasticity in a mouse model of metachromatic leukodystrophy, a human lysosomal storage disorder
Authors: Faldini, Enrico
Stroobants, Stijn
Balschun, Detlef
D'Hooge, Rudi #
Issue Date: Jul-2010
Host Document: FENS abstract vol:5
Conference: FENS Forum of European Neuroscience edition:7 location:Amsterdam date:3 - 7 July 2010
Article number: 109.8
Abstract: Knockout mice deficient for the lysosomal enzyme arylsulfatase A (ASA) constitute an animal model of the neurodegenerative neurolipidosis, metachromatic leukodystrophy. Although cognitive decline is part of all forms of the human disease, previous behavioural studies on the mouse model failed to provide evidence for ataxia-unrelated deficits in learning/memory tasks before 1 year of age.
In the present study, we firstly examined 6-month-old ASA-/- mice in a T-maze delayed alternation task (TMDAT), a paradigm that is well suited to test cognition in mice while not being motorically demanding. In this task mice need to remember the arm visited during an initial trial, to correctly visit the baited alternate arm in the test trial. Although ASA-deficient mice eventually reached the same peak performance level (~100% correct), they generally made more errors than wildtype control mice (p<0.05). These results make clear that ASA-/- mice display a significant short-term working-memory deficit in TMDAT.
Since TMDAT is known to depend on proper hippocampal operation, it was tempting to investigate whether this cognitive deficit was accompanied by a deterioration of hippocampal short- and long-term plasticity. Extracellular recordings in the CA1-region of the hippocampus did not show significant differences between ASA -/- mice and controls in basic synaptic properties and short-term plasticity as evaluated by input-output curves and paired-pulse stimulation at different interpulse intervals. In contrast, ASA-/- mice were significantly impaired in the induction of long-term potentiation. Thus, a single theta-burst stimulation (10 trains of 4 burst of 4 stimuli at 100 Hz) induced only an LTP of 156 ± 5% in ASA-/- mice, but a potentiation of 178 ± 6% in ASA +/- and of 183 ± 6 % in WT littermates. This difference was maintained throughout the recording period of 4 hours (p< 0.001 repeated measures ANOVA).
These behavioural and electrophysiological findings indicate that the murine model mimics the neurocognitive phenotype of the human disease and can be used in preclinical therapeutic studies.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Biological Psychology
# (joint) last author

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