Title: Neuronal migration depends on intact peroxisomal function in brain and in extraneuronal tissues
Authors: Janssen, Anneleen
Gressens, Pierre
Grabenbauer, Markus
Baumgart, Eveline
Schad, Arno
Vanhorebeek, Ilse
Brouwers, Annelies
Declercq, Peter E
Fahimi, Dariush
Evrard, Philippe
Schoonjans, Luc
Collen, Desire
Carmeliet, Peter
Mannaerts, Guy
Van Veldhoven, Paul P
Baes, Myriam # ×
Issue Date: Oct-2003
Publisher: Soc neuroscience
Series Title: Journal of Neuroscience vol:23 issue:30 pages:9732-9741
Abstract: Functional peroxisome deficiency, as encountered in Zellweger syndrome, causes a specific impairment of neuronal migration. Although the molecular mechanisms underlying the neuronal migration defect are at present unknown, the excess of very long chain fatty acids in brain, a consequence of peroxisomal beta-oxidation deficiency, has often been hypothesized to play a major role. The purpose of the present study was to investigate the contribution of peroxisomal dysfunction in brain as opposed to peroxisomal dysfunction in extraneuronal tissues to the migration defect. Peroxisomes were selectively reconstituted either in brain or liver of Pex5 knock-out mice, a model for Zellweger syndrome, by tissue-selective overexpression of Pex5p. We found that both rescue strains exhibited a significant correction of the neuronal migration defect despite an incomplete reconstitution of peroxisomal function in the targeted tissue. Animals with a simultaneous rescue of peroxisomes in both tissues displayed a pattern of neuronal migration indistinguishable from that of wild-type animals on the basis of cresyl violet staining and 5', 3'-bromo-2'-deoxyuridine birth-dating analysis. These data suggest that peroxisomal metabolism in brain but also in extraneuronal tissues affects the normal development of the mouse neocortex. In liver-rescued mice, the improvement of the neuronal migration was not accompanied by changes in very long chain fatty acid, docosahexaenoic acid, or plasmalogen levels in brain, indicating that other metabolic factors can influence the neuronal migration process.
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pharmacology Section (-)
Molecular and Vascular Biology
Cell Metabolism
Laboratory of Intensive Care Medicine
Laboratory of Lipid Biochemistry and Protein Interactions
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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