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

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Abstract

Dementia is a frequent complication of Parkinson’s 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-α-synuclein, anti-brain-derived neurotrophic factor (BDNF), and anti-glial fibrillary acidic protein antibodies. In addition, the mRNA expressions of cytokines (IL-1α, IL-1β, TNF-α, IL-6, TGF-β) 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.

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Authors and Affiliations

  1. Department of Neurology, Okazaki City Hospital, 3-1 Goshoai, Kouryuuji-cho, 444-8553, Okazaki, Aichi, Japan

    Kazuhiro Imamura

  2. Department of Neurology, Nagoya University School of Medicine, Nagoya, Aichi, Japan

    Nozomi Hishikawa

  3. Institute for Comprehensive Medical Science, Fujita Health University, Japan Science and Technology Corporation, Toyoake, Aichi, Japan

    Kenji Ono, Hiromi Suzuki, Makoto Sawada & Toshiharu Nagatsu

  4. Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan

    Mari Yoshida & Yoshio Hashizume

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  1. Kazuhiro Imamura
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  2. Nozomi Hishikawa
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  3. Kenji Ono
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  4. Hiromi Suzuki
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  5. Makoto Sawada
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  6. Toshiharu Nagatsu
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  7. Mari Yoshida
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Correspondence to Kazuhiro Imamura.

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Imamura, K., Hishikawa, N., Ono, K. et al. Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol 109, 141–150 (2005). https://doi.org/10.1007/s00401-004-0919-y

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