Neuronal migration disorder in Zellweger mice is secondary to glutamate receptor dysfunction.

Abstract

Disorders of neuronal migration in cerebral cortex are associated with neurological impairments, including mental retardation and epilepsy. Their causes and pathophysiology remain largely unknown, however. In patients with Zellweger disease, a lethal panperoxisomal disorder, and in mice lacking the Pxr1 import receptor for peroxisomal matrix proteins, the absence of peroxisomes leads to abnormal neuronal migration. Analysis of Pxr1-/- mice revealed that the migration defect was caused by altered N-methyl-D-aspartate (NMDA) glutamate receptor-mediated calcium mobilization. This NMDA receptor dysfunction was linked to a deficit in platelet-activating factor, a phenomenon related to peroxisome impairment. These findings confirm NMDA receptor involvement in neuronal migration and suggest a link between peroxisome metabolism and NMDA receptor efficacy.

• Authors: P Gressens, M Baes, P Leroux, A Lombet, P Van Veldhoven, A Janssen, J Vamecq, S Marret, P Evrard
• Journal: Annals of neurology (Ann Neurol) Vol. 48 Issue 3 Pg. 336-43 (Sep 2000) ISSN: 0364-5134 [Print] United States
• PMID: 10976640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, GABA
• Receptors, Glutamate
• Receptors, N-Methyl-D-Aspartate
• Dizocilpine Maleate
• Calcium

Topics

• Animals
• Autoradiography
• Calcium (metabolism)
• Cell Movement (physiology)
• Dizocilpine Maleate (pharmacology)
• Female
• Male
• Mice
• Neurons (metabolism, physiology)
• Receptors, GABA (metabolism)
• Receptors, Glutamate (physiology)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Zellweger Syndrome (metabolism, physiopathology)