Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease.

Abstract

Wilson's disease (WD) is caused by mutations in the copper transporting ATPase 7B (Atp7b). Patients present with liver pathology or behavioural disturbances. Studies on rodent models for WD so far mainly focussed on liver, not brain. The effect of knockout of atp7b on sensori-motor and cognitive behaviour, as well as neuronal number, inflammatory markers, copper and synaptic proteins in brain were studied in so-called toxic milk mice. Copper accumulated in striatum and hippocampus of toxic milk mice, but not in cerebral cortex. Inflammatory markers were increased in striatum and corpus callosum, but not in cerebral cortex and hippocampus, whereas neuronal numbers were unchanged. Toxic milk mice were mildly impaired in the rotarod and cylinder test and unable to acquire spatial memory in the Morris water maze. Despite the latter observation only synaptophysin of a number of synaptic proteins, was altered in the hippocampus of toxic milk mice. In addition to disturbances in neuronal signalling by increased brain copper, inflammation and inflammatory signalling from the periphery to the brain might add to the behavioural disturbances in the toxic milk mice. These mice can be used to evaluate therapeutic strategies to alleviate behavioural disturbances and cerebral pathology observed in WD.

• Authors: Dick Terwel, Yi-Na Löschmann, Hartmut H-J Schmidt, Hans R Schöler, Tobias Cantz, Michael T Heneka
• Journal: Journal of neurochemistry (J Neurochem) Vol. 118 Issue 1 Pg. 105-12 (Jul 2011) ISSN: 1471-4159 [Electronic] England
• PMID: 21517843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Chemical References

• Atp7a protein, mouse
• CD11b Antigen
• Cation Transport Proteins
• Cytokines
• Glial Fibrillary Acidic Protein
• Copper
• Adenosine Triphosphatases
• Phosphopyruvate Hydratase
• Copper-Transporting ATPases

Topics

• Adenosine Triphosphatases (genetics)
• Analysis of Variance
• Animals
• Behavior, Animal (physiology)
• Brain (metabolism)
• CD11b Antigen (metabolism)
• Cation Transport Proteins (genetics)
• Copper (metabolism)
• Copper-Transporting ATPases
• Cytokines (blood, genetics)
• Disease Models, Animal
• Encephalitis (etiology, genetics)
• Exploratory Behavior
• Female
• Glial Fibrillary Acidic Protein (metabolism)
• Hand Strength (physiology)
• Hepatolenticular Degeneration (complications, genetics, pathology)
• Liver (pathology)
• Male
• Maze Learning (physiology)
• Mice
• Mice, Transgenic
• Milk (toxicity)
• Motor Activity (genetics)
• Mutation (genetics)
• Phosphopyruvate Hydratase (metabolism)
• Psychomotor Performance (physiology)