Immunolocalization of glutaryl-CoA dehydrogenase (GCDH) in adult and embryonic rat brain and peripheral tissues. (20th February 2017)

• Record Type: Journal Article
• Authors: Braissant, Olivier; Jafari, Paris; Remacle, Noémie; Cudré-Cung, Hong-Phuc; Do Vale Pereira, Sonia; Ballhausen, Diana
• Is Part Of: Neuroscience. Volume 343(2017)
• Page Start: 355
• Page End: 363
• Publication Date: 2017-02-20
• Subjects: 1H-MRS proton magnetic resonance spectroscopy -- 3-OHGA 3-hydroxyglutaric acid -- BBB blood brain barrier -- BSA bovine serum albumin -- CNS central nervous system -- DEPC diethyl-pyrocarbonate -- GA glutaric acid -- GA-I glutaric aciduria type I -- GalC galactocerebroside -- GCDH glutaryl-CoA dehydrogenase -- GFAP glial fibrillary acidic protein -- KO knockout -- MAP-2 microtubule-associated protein 2 -- MBP myelin basic protein -- MRI magnetic resonance imaging -- MRPL12 mitochondrial ribosomal protein L12 -- NaDC3 sodium-dependent dicarboxylate transporter 3 -- NeuN neuronal nuclei protein -- OAT1 organic anion transporter 1 -- PBS phosphate buffer saline -- PFA paraformaldehyde -- p-NFM phosphorylated medium weight neurofilament; glutaryl-CoA-dehydrogenase -- expression -- glutaric aciduria type-I -- rat tissues -- embryonic development -- central and peripheral nervous system; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.10.049
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: GCDH is widely expressed in embryonic and adult rat tissues. A high GCDH expression in embryonic rat brain suggests an important role in brain development and function. GCDH is strongly expressed in proximal tubules of the kidney. A significant GCDH expression was found in epithelial cells. 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.