title: Neuropathological analysis in spinal muscular atrophy type II.
abstract: We performed a neuropathological analysis, including in situ nick end labeling (ISEL) and immunohistochemistry, of two cases of clinicogenetically confirmed infantile spinal muscular atrophy (SMA) type II. Both cases showed severe reduction of the motor neurons and gliosis in the spinal cord and brain stem, although the occurrences of central chromatolysis and ballooned neurons were not frequent. Clark's and lateral thalamic nuclei, which are usually altered in SMA type I, were spared, whereas Betz cells in the precentral gyrus and large myelinated fibers in the lateral funiculus were reduced in number. Regarding apoptosis, only the younger case demonstrated a few ISEL-positive nuclei in the dorsal horn, with reduced Bcl-x expression level in the Purkinje cells. Unlike SMA type I, the expression of neurofilaments was not disturbed and the reduction in synaptophysin expression level in the anterior horn was mild. An oxidative stress-related product was deposited in atrophic motor neurons in the spinal cord, and neurons with nuclei immunoreactive for 8-hydroxy-2'-deoxyguanosine were found in the lateral thalamus. In contrast, the expression of glial glutamate transporters was not altered. These data suggest that oxidative stress and, to a lesser extent, apoptotic cell death, but not disturbed neurofilament metabolism or excitotoxicity, may be involved in neurodegeneration in SMA type II.
authors.affiliation: Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashi-dai, Fuchu-shi, 183-0042, Tokyo, Japan. arakis@tmnh.fuchu.tokyo.jp
authors.forename: S
authors.initials: S
authors.lastname: Araki
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Tamagawa
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Komori
authors.forename: Y
authors.initials: Y
authors.lastname: Sakakihara
authors.forename: T
authors.initials: T
authors.lastname: Mizutani
authors.forename: M
authors.initials: M
authors.lastname: Oda
mesh_terms: D000328:Adult; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D003839:Deoxyadenosines / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005091:Exons; D005260:Female; D005911:Gliosis; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism / Q000473:pathology
chemical_list: C436623:8-hydroxy-2'-deoxyadenosine; D027322:Amino Acid Transport System X-AG; D003839:Deoxyadenosines; D027342:Excitatory Amino Acid Transporter 2; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016708:Synaptophysin