title: Cerebellar neurodegeneration in human hereditary DNA repair disorders.
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.
authors.affiliation: Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kohji
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Shioda
authors.forename: M
authors.initials: M
authors.lastname: Minagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Morimatsu
authors.forename: K
authors.initials: K
authors.lastname: Tamagawa
authors.forename: M
authors.initials: M
authors.lastname: Oda
mesh_terms: D000293:Adolescent; D000328:Adult; D001710:Biotin; D001923:Brain Chemistry; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology*; D002648:Child; D003057:Cockayne Syndrome / Q000235:genetics / Q000473:pathology*; D053938:DNA Fragmentation; D004260:DNA Repair; D003856:Deoxyuracil Nucleotides; D005260:Female; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D018696:Neuroprotective Agents / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000473:pathology*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D003856:Deoxyuracil Nucleotides; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001710:Biotin; D020794:Receptor Protein-Tyrosine Kinases