Abstract
Recent findings have focused attention on the role of apoptosis in neurodegenerative diseases, however, the apoptotic process in child-onset brain disorders has been little investigated. Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are hereditary disorders characterized by impaired DNA repair and neurodegeneration. We investigated apoptotic cell death in the cerebellum of five cases of XP group A (XPA), four cases of CS, and twelve controls, using TdT-mediated DIG-dUTP nick-end labeling (TUNEL) and immunohistochemical staining for bcl-2, bcl-x, p53, bax, BDNF and Trk B. The TUNEL-positive cells were found in the granule cells of the cerebellar cortex of two patients with XPA and two patients with CS, whereas such cells were not detected in the cerebellar cortex in controls. Upregulation of bcl-2 or BDNF was not observed, and bcl-x expression was not altered. Some patients showed nuclear expression of p53 in the granule cells and/or molecular layer, bax-positive glial cells in the cerebellar white matter, and a few Trk B-positive cells in the granular layer. These findings suggest that apoptotic cell death can be involved in the cerebellar degeneration in patients with hereditary defects in DNA repair mechanisms.
References
Aug 1, 1995·Neuropathology and Applied Neurobiology·D W EllisonR O Weller
Nov 1, 1994·Journal of Neuropathology and Experimental Neurology·A MigheliD Schiffer
Sep 14, 1995·Nature·H NakaneY Kitamura
Oct 3, 1994·Neuroreport·A MigheliD Schiffer
Sep 17, 1993·Brain Research·X F ZhouR A Rush
May 1, 1996·The Journal of Cell Biology·I Neveu, E Arenas
Dec 1, 1995·Neuropathology and Applied Neurobiology·D TroostJ M de Jong
Jan 1, 1996·Annual Review of Biochemistry·A Sancar
Oct 1, 1996·Brain Pathology·C W Cotman, J H Su
Nov 1, 1996·Virchows Archiv : an International Journal of Pathology·A HaraH Mori
Jan 1, 1997·Journal of Neuropathology and Experimental Neurology·J H SuC W Cotman
May 2, 1997·Cell·G T van der HorstJ H Hoeijmakers
Citations
Mar 12, 2004·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Anand K KondapiK Subba Rao
Jul 21, 1999·Brain & Development·M ItohM Oda
Aug 3, 2010·Antioxidants & Redox Signaling·Gordon P McCallumPeter G Wells
Jan 22, 2009·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Masaharu Hayashi
Nov 10, 2006·Journal of Child Neurology·Isabelle RapinDennis W Dickson
Nov 21, 2013·Acta Neuropathologica Communications·Jin-Ping LaiKenneth H Kraemer
Dec 17, 2011·PLoS Genetics·Dick JaarsmaGijsbertus T J van der Horst
Apr 3, 2012·Journal of Neurosurgery·Gregor TomasevicTracy K McIntosh
Nov 1, 2001·Proceedings of the National Academy of Sciences of the United States of America·M MuraiH Hatanaka
Jan 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·R R LaposaJ E Cleaver
Dec 1, 2015·Aging Cell·Chunlian LiuBaisong Lu
Jul 26, 2011·Brain & Development·Masaharu HayashiRyo Fukatsu
May 10, 2011·Progress in Neurobiology·Dennis Kjølhede JeppesenTinna Stevnsner
Aug 4, 2009·Mechanisms of Ageing and Development·Karen M WeidenheimIsabelle Rapin
Jun 10, 2008·Mechanisms of Ageing and Development·Laura J Niedernhofer
Feb 15, 2008·DNA Repair·Laura J Niedernhofer
Mar 14, 2008·Mechanisms of Ageing and Development·J E Cleaver, I Revet
Jan 15, 2004·Journal of Neurochemistry·F Fonnum, E A Lock
Sep 1, 2004·Brain Research. Molecular Brain Research·Elizabeth JacobsenYung Chang
Jan 1, 2005·Brain & Development·Masaharu HayashiRyo Fukatsu
Dec 17, 2014·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Hiroaki MiyaharaKenji Ihara
Oct 26, 1999·The Journal of Biological Chemistry·E AlberdiS P Becerra
Aug 13, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Christian Lesuisse, Lee J Martin
Dec 14, 2017·The Journal of Cell Biology·Shalaka Chitale, Holger Richly
Mar 30, 2001·Cell Death and Differentiation·R S Morrison, Y Kinoshita
Nov 13, 2004·Journal of Neuropathology and Experimental Neurology·Masaharu HayashiKimiko Tamagawa
Apr 18, 2001·Journal of Neuropathology and Experimental Neurology·M HayashiM Oda