title: 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.affiliation: INSERM E 9935 and Service de Neurologie Pédiatrique, Hôpital Robert-Debré, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Gressens
authors.forename: M
authors.initials: M
authors.lastname: Baes
authors.forename: P
authors.initials: P
authors.lastname: Leroux
authors.forename: A
authors.initials: A
authors.lastname: Lombet
authors.forename: P
authors.initials: P
authors.lastname: Van Veldhoven
authors.forename: A
authors.initials: A
authors.lastname: Janssen
authors.forename: J
authors.initials: J
authors.lastname: Vamecq
authors.forename: S
authors.initials: S
authors.lastname: Marret
authors.forename: P
authors.initials: P
authors.lastname: Evrard
mesh_terms: D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015211:Zellweger Syndrome / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D018079:Receptors, GABA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002118:Calcium