Hyperactivity, neuromotor defects, and impaired learning and memory in a mouse model for metachromatic leukodystrophy

Deficiency of arylsulfatase A (ASA) causes the autosomal recessive lipidosi s, metachromatic leukodystrophy (MLD). Performance on tests of activity, mo tor ability and learning/memory was assessed in ASA-deficient mice and norm al controls at 3, 6 and 12 months-of-age. ASA-deficient mice showed consist ently increased cage activity in all age groups. whereas open field activit y was increased only in the 3-month-old group. Motor coordination and equil ibrium, as tested in the rotarod test, was impaired in 12-month-old ASA-def icient mice. Passive avoidance learning was tested in the step-through box. Performance on this test was impaired in the 12-month-old group only. Spat ial learning and memory abilities were tested in the Morris water maze. Six -month-old ASA-deficient mice displayed slightly impaired hidden-platform a cquisition performance. Three-month-old animals, on the other hand, did not show any acquisition or retention defect on this task, notwithstanding sig nificantly reduced swimming velocity. Acquisition training, both in the hid den- and visible-platform conditions of the Morris water maze, and retentio n performance during the probe trials were impaired in 12-month-old ASA-def icient mice. The hyperactivity, motor incoordination and slowing, and the a ge-related learning/memory defects, reported here in ASA-deficient mice, ma y relate to the decline of neuromotor and cognitive functions in MLD patien ts, and could be used as correlative or outcome measures in the study of ML D pathophysiology and treatment. (C) 2001 Elsevier Science B.V. All rights reserved.