Acta Neuropathologica

, Volume 109, Issue 2, pp 141–150

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

  • Kazuhiro Imamura
  • Nozomi Hishikawa
  • Kenji Ono
  • Hiromi Suzuki
  • Makoto Sawada
  • Toshiharu Nagatsu
  • Mari Yoshida
  • Yoshio Hashizume
Regular Paper

DOI: 10.1007/s00401-004-0919-y

Cite this article as:
Imamura, K., Hishikawa, N., Ono, K. et al. Acta Neuropathol (2005) 109: 141. doi:10.1007/s00401-004-0919-y

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.

Keywords

Lewy body diseaseMicrogliaMajor histocompatibility complex class II antigenInterleukin-6Brain-derived neurotrophic factor

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Kazuhiro Imamura
    • 1
  • Nozomi Hishikawa
    • 2
  • Kenji Ono
    • 3
  • Hiromi Suzuki
    • 3
  • Makoto Sawada
    • 3
  • Toshiharu Nagatsu
    • 3
  • Mari Yoshida
    • 4
  • Yoshio Hashizume
    • 4
  1. 1.Department of NeurologyOkazaki City HospitalOkazakiJapan
  2. 2.Department of NeurologyNagoya University School of MedicineNagoyaJapan
  3. 3.Institute for Comprehensive Medical ScienceFujita Health University, Japan Science and Technology CorporationToyoakeJapan
  4. 4.Department of Neuropathology, Institute for Medical Science of AgingAichi Medical UniversityNagakuteJapan