title: Immunolocalization of glutaryl-CoA dehydrogenase (GCDH) in adult and embryonic rat brain and peripheral tissues.
abstract: Glutaryl-CoA dehydrogenase (GCDH) is a mitochondrial enzyme that is involved in the degradation of tryptophan, lysine and hydroxylysine. Deficient enzyme activity leads to glutaric aciduria type-I (GA-I). This neurometabolic disease usually manifests with acute encephalopathic crises and striatal neuronal death in early childhood leading to an irreversible dystonic-dyskinetic movement disorder. Fronto-temporal atrophy and white matter changes are already present in the pre-symptomatic period. No detailed information on GCDH expression during embryonic development and in adulthood was available so far. Using immunofluorescence microscopy and cell-type-specific markers to localize GCDH in different tissues, we describe the differential cellular localization of GCDH in adult rat brain and peripheral organs as well as its spatiotemporal expression pattern. During embryonic development GCDH was predominantly expressed in neurons of the central and peripheral nervous system. Significant expression levels were found in epithelial cells (skin, intestinal and nasal mucosa) of rat embryos at different developmental stages. Besides the expected strong expression in liver, GCDH was found to be significantly expressed in neurons of different brain regions, renal proximal tubules, intestinal mucosa and peripheral nerves of adult rats. GCDH was found widely expressed in embryonic and adult rat tissues. In rat embryos GCDH is predominantly expressed in brain implying an important role for brain development. Interestingly, GCDH was found to be significantly expressed in different other organs (e.g. kidney, gut) in adult rats probably explaining the evolving phenotype in GA-I patients.
authors.affiliation: Inborn Errors of Metabolism, Biomedicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: olivier.braissant@chuv.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Braissant
authors.affiliation: Inborn Errors of Metabolism, Center for Molecular Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: paris.jafari@chuv.ch.
authors.forename: Paris
authors.initials: P
authors.lastname: Jafari
authors.affiliation: Inborn Errors of Metabolism, Center for Molecular Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: noemie.remacle@chuv.ch.
authors.forename: Noémie
authors.initials: N
authors.lastname: Remacle
authors.affiliation: Inborn Errors of Metabolism, Center for Molecular Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: thanh-hong-phuc.cung@chuv.ch.
authors.forename: Hong-Phuc
authors.initials: HP
authors.lastname: Cudré-Cung
authors.affiliation: Inborn Errors of Metabolism, Center for Molecular Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: svalpereira@gmail.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Do Vale Pereira
authors.affiliation: Inborn Errors of Metabolism, Center for Molecular Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: diana.ballhausen@chuv.ch.
authors.forename: Diana
authors.initials: D
authors.lastname: Ballhausen
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D005260:Female; D005455:Fluorescent Antibody Technique; D050770:Glutaryl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D007668:Kidney / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D024510:Muscle Development / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D017207:Rats, Sprague-Dawley
chemical_list: D050770:Glutaryl-CoA Dehydrogenase
keywords: central and peripheral nervous system; embryonic development; expression; glutaric aciduria type-I; glutaryl-CoA-dehydrogenase; rat tissues