title: Neuromotor alterations and cerebellar deficits in aged arylsulfatase A-deficient transgenic mice.
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.
authors.affiliation: Laboratory of Neurochemistry and Behavior at Born-Bunge Foundation, University of Antwerp1, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: D'Hooge
authors.forename: D
authors.initials: D
authors.lastname: Hartmann
authors.forename: J
authors.initials: J
authors.lastname: Manil
authors.forename: F
authors.initials: F
authors.lastname: Colin
authors.forename: V
authors.initials: V
authors.lastname: Gieselmann
authors.forename: P P
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D064026:Calbindins; D002526:Cerebellar Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism; D002553:Cerebroside-Sulfatase / Q000172:deficiency* / Q000235:genetics; D003712:Dendrites / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009043:Motor Activity; D011597:Psychomotor Performance; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D002553:Cerebroside-Sulfatase