Evidence for central nervous system glial cell plasticity in phenylketonuria

Journal of Neuropathology and Experimental Neurology
C A DyerH L Levy

Abstract

Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. The primary pathologic finding is hypomyelination and gliosis of central nervous system white matter. Similar white matter pathology is observed in the Pahenu2 mouse, a genetic model for PKU. We studied this mouse to examine the basis for these neuropathologic changes in PKU and to determine if hypomyelination and gliosis occur independently or are interrelated. Although white matter tracts within PKU brains are hypomyelinated, immunostaining and Western blot analyses revealed that these tracts contain abundant amounts of myelin markers, i.e. myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'phosphohydrolase, and myelin/oligodendrocyte-specific protein (MOSP). However, Western blot analyses also showed that MBP isoform expression was aberrant. Investigation of individual cells was performed by extraction of tissue sections with Triton X-100. Most of the MOSP was extracted, with the remaining MOSP clearly visible in dual labeled cells, i.e. MOSP was colocalized along glial fibrillary acidic protein (GFAP) filaments. Cells expressing both MBP and GFA...Continue Reading

Citations

Jul 5, 2005·Journal of Neurology·Belén Pérez-DueñasJaume Campistol
Apr 9, 2008·Journal of Inherited Metabolic Disease·S KölkerJ G Okun
Feb 13, 2010·Journal of Inherited Metabolic Disease·Renaud SchoemansVincent Bours
Apr 6, 2007·Neuropsychology Review·J J MoyleJ R Burnett
Jan 26, 2002·Behavioural Brain Research·W T O'BrienR J Servatius
Sep 20, 2005·The Australian and New Zealand Journal of Psychiatry·Mark WalterfangChristos Pantelis
Mar 22, 2006·Pediatric Research·Friederike HörsterStefan Kins
Jan 6, 2001·Developmental Neuropsychology·M T BanichR D Steiner
Feb 5, 2009·Journal of Inherited Metabolic Disease·F J van SpronsenDirk-Jan Reijngoud
Apr 24, 2007·Progress in Neurobiology·Jessica CarmenMark P Mattson
Jul 16, 2003·Journal of Neurochemistry·Bernadin Joseph, Charissa A Dyer
Aug 1, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Cécile FlignyFrancine Côté
Jun 25, 2015·Frontiers in Neuroanatomy·Badrah Alghamdi, Robert Fern
Oct 10, 2014·Human Molecular Genetics·Katja HorlingGabriele M Rune
Mar 28, 2017·Neurología : publicación oficial de la Sociedad Española de Neurología·U Gómez-PinedoJ Matias-Guiu
Jun 22, 2005·Glia·Diane M Studzinski, Joyce A Benjamins
Feb 15, 2002·Journal of the International Neuropsychological Society : JINS·Desirée A WhiteRobert D Steiner
Jun 24, 2000·Journal of the Experimental Analysis of Behavior·S M MihalickW V Dube
Dec 31, 1998·Current Opinion in Neurology·J Pietz
Mar 7, 2020·Journal of Neuroscience Research·Bruna Klippel FerreiraPatricia Fernanda Schuck
Oct 6, 2001·Annals of Clinical Biochemistry·M Cleary, J H Walter
May 8, 2000·Journal of Neuroscience Research·C A DyerJ Kamholz
May 22, 2021·Nature Reviews. Disease Primers·Francjan J van SpronsenAnnet M Bosch

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