Elsevier

Neuroscience Letters

Volume 273, Issue 2, 1 October 1999, Pages 93-96
Neuroscience Letters

Neuromotor alterations and cerebellar deficits in aged arylsulfatase A-deficient transgenic mice

https://doi.org/10.1016/S0304-3940(99)00647-3Get rights and content

Abstract

Arylsulfatase A (ASA)-deficient (−/−) mice and ASA(+/+) controls were constructed as a transgenic model for the lysosomal storage disease, metachromatic leukodystrophy (MLD). One-year-old ASA(−/−) mice showed impaired rotarod performance and altered walking pattern characterized by a shorter pace, later evolving into more severe ataxia with tremor in 2-year-old mice. Examination of cerebellar histology showed that 2-year-old ASA(−/−) mice have lost most of the calbindin immunoreactivity from their Purkinje cell dendrites and show simplified dendritic architecture. Additionally, ASA-deficient mice lost a substantial proportion of their Purkinje cells. Recordings of unitary potentials and stimulation of climbing fibers on cerebellar slices from 2-year-old mice indicated that, although the main cerebellar synapses seem to be present and functioning physiologically, the climbing fibers of ASA-deficient mice may have enhanced effects on Purkinje cell activity. It is concluded that ambulatory dysfunctions in ASA(−/−) mice might be explained by an imbalance in the consequences of climbing fiber signals upon Purkinje cell activity due to selective neurodegeneration within the cerebellum.

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Acknowledgements

We thank Dagmar Niemeyer, Frieda Frank and Monika Grell for technical assistance. Financial support was obtained from Born–Bunge Foundation, OCMW Medical Research Foundation, NeuroSearch Antwerp, FWO-Flanders (Grant No. G.0027.97), Antwerp University and Deutsche Forschungsgemeinschaft DFG (Grant No. Lu172/8–1). Dr Rudi D'Hooge is a postdoctoral fellow of FWO-Flanders.

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