Neurodegenerative mechanisms in subacute sclerosing panencephalitis.
Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated measles virus, showing inflammation, neuronal loss, and demyelination. We neuropathologically examined six autopsy cases of subacute sclerosing panencephalitis, using in situ nick end-labeling and immunohistochemistry. Both the neurons and glial cells in the cerebral cortex showed immunoreactive nuclei in the nick end-labeling in two cases with disease duration within 2 years, whereas they were confined to the glial cells in the demyelinated cerebral white matter in three cases with disease duration ranging from 2 to 10 years. The nuclei and cytoplasm were immunoreactive for 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine, markers of oxidative damage to DNA and ribonucleic acid, respectively, in the cerebral cortex in three cases with disease duration within 9 years. In contrast, 4-hydroxy-2-nonenal-modified proteins, products of lipid peroxidation, were deposited in the demyelinated white matters in four cases with disease duration longer than 9 years. In three cases with long survival, the expression of glial glutamate transporters was reduced in the cerebral cortex. It is speculated in subacute sclerosing panencephalitis that apoptosis and oxidative stress to DNA can contribute to the early neuronal damage, whereas lipid peroxidation and disturbed glutamate transport may be related to the subsequent neurodegeneration.
Hayashi
Masaharu
M
Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu-shi, Tokyo, Japan. mahayasi@tmin.ac.jp
Arai
Nobutaka
N
Satoh
Junichi
J
Suzuki
Hisaharu
H
Katayama
Kazunobu
K
Tamagawa
Kimiko
K
Morimatsu
Yoshio
Y
D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D001344:Autopsy; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D013344:Subacute Sclerosing Panencephalitis / Q000378:metabolism*; D013997:Time Factors
D000447:Aldehydes; D027322:Amino Acid Transport System X-AG; D006151:Guanosine; C046215:8-hydroxyguanosine; C027576:4-hydroxy-2-nonenal