Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies.
Glial involvement in the degeneration process of Lewy body (LB)-bearing neurons and the degradation process of LBs in the cerebral cortex and amygdala in brains of dementia with Lewy bodies was investigated immunohistochemically. HLA-DR-positive microglia frequently extended their processes to degenerated neurons with alpha-synuclein-positive LBs, while some GFAP-positive astroglial processes attached to weakly alpha-synuclein-positive extracellular LBs. Some intracellular LBs were immunoreactive to anti-C4d antibody, and these LB-bearing neurons were involved by activated microglia. About half of the intracellular LBs were immunoreactive to anti-chromogranin-A (CGA) antibody, and most of CGA-positive LB-bearing neurons were surrounded by microglia. Although we could find no evident participation of TNF-alpha, a candidate cytokine that is up-regulated by microglia following CGA stimulation, in the degeneration process of LB-bearing neurons, some intracellular LBs were immunoreactive to the antibody to NF-kappaB, a transcriptional factor activated by cytokines. These findings suggest that microglia participate in the degeneration process of LB-bearing neurons via varying immunogenic elements including complement proteins, CGA and probably some cytokines, and that astroglia participate in the degradation process of LBs.
Togo
T
T
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Iseki
E
E
Marui
W
W
Akiyama
H
H
Uéda
K
K
Kosaka
K
K
D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051843:Synucleins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051844:alpha-Synuclein
D053379:Chromogranin A; D002864:Chromogranins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein