Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains

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• 作者：Kazuhiro Imamura ; Nozomi Hishikawa ; Kenji Ono ; Hiromi Suzuki ; Makoto Sawada ; Toshiharu Nagatsu ; Mari Yoshida and Yoshio Hashizume
• 关键词：Lewy body disease ; Microglia ; Major histocompatibility complex class II antigen ; Interleukin ; 6 ; Brain ; derived neurotrophic factor
• 刊名：Acta Neuropathologica
• 出版年：2005
• 出版时间：February 2005
• 年：2005
• 卷：109
• 期：2
• 页码：141-150
• 全文大小：638 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pathology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0533

文摘

Dementia is a frequent complication of Parkinsons disease (PD) and usually occurs late in the protracted course of the illness. We have already reported numerous MHC class II-positive microglia in the hippocampus in PD patients, and that this phenomenon may be responsible for functional changes in the neurons and the cognitive decline in PD patients. In this study, we have investigated the distribution of activated microglia and the immunohistochemical and the mRNA expression of several cytokines and neurotrophic factors of the hippocampus in PD and dementia with Lewy bodies (DLB). The brains from five cases of PD and five cases of DLB that were clinically and neuropathologically diagnosed, and those from four normal controls (NC) were evaluated by immunohistochemistry using anti-HLA-DP, -DQ, -DR (CR3/43), anti--synuclein, anti-brain-derived neurotrophic factor (BDNF), and anti-glial fibrillary acidic protein antibodies. In addition, the mRNA expressions of cytokines (IL-1, IL-1, TNF-, IL-6, TGF-) and neurotrophic factors (BDNF, GDNF, NGF, NT-3) of these brains were evaluated by the reverse transcription-PCR method. MHC class II-positive microglia were distributed diffusely in the hippocampus of PD and DLB brains. Although the cytoplasm of pyramidal and granular cells of the hippocampus in NC brains was strongly stained by anti-BDNF antibodies, it was only weakly stained in PD and DLB brains. The mRNA expression of IL-6 was significantly increased in the hippocampus of PD and DLB brains, and that of BDNF was significantly decreased in the hippocampus of DLB brains. The increased number of activated microglia and the production of neurotrophic cytokines such as IL-6, together with the decreased expression of the neurotrophic factors of neurons in the hippocampus of PD and DLB brains, may be related to functional cellular changes associated with dementia.