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

Brain Res. 2001 Jul 13;907(1-2):35-43. doi: 10.1016/s0006-8993(01)02374-5.


Deficiency of arylsulfatase A (ASA) causes the autosomal recessive lipidosis, metachromatic leukodystrophy (MLD). Performance on tests of activity, motor ability and learning/memory was assessed in ASA-deficient mice and normal controls at 3, 6 and 12 months-of-age. ASA-deficient mice showed consistently increased cage activity in all age groups, whereas open field activity was increased only in the 3-month-old group. Motor coordination and equilibrium, as tested in the rotarod test, was impaired in 12-month-old ASA-deficient mice. Passive avoidance learning was tested in the step-through box. Performance on this test was impaired in the 12-month-old group only. Spatial learning and memory abilities were tested in the Morris water maze. Six-month-old ASA-deficient mice displayed slightly impaired hidden-platform acquisition performance. Three-month-old animals, on the other hand, did not show any acquisition or retention defect on this task, notwithstanding significantly reduced swimming velocity. Acquisition training, both in the hidden- and visible-platform conditions of the Morris water maze, and retention performance during the probe trials were impaired in 12-month-old ASA-deficient mice. The hyperactivity, motor incoordination and slowing, and the age-related learning/memory defects, reported here in ASA-deficient mice, may relate to the decline of neuromotor and cognitive functions in MLD patients, and could be used as correlative or outcome measures in the study of MLD pathophysiology and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Avoidance Learning
  • Cerebroside-Sulfatase / deficiency*
  • Cerebroside-Sulfatase / genetics
  • Cerebroside-Sulfatase / physiology
  • Exploratory Behavior
  • Genotype
  • Hyperkinesis / genetics*
  • Learning Disabilities / genetics*
  • Leukodystrophy, Metachromatic / genetics
  • Leukodystrophy, Metachromatic / physiopathology*
  • Leukodystrophy, Metachromatic / psychology
  • Maze Learning
  • Memory Disorders / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Motor Skills Disorders / genetics*
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Psychomotor Performance
  • Retention, Psychology
  • Spatial Behavior
  • Swimming


  • Nerve Tissue Proteins
  • Cerebroside-Sulfatase