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

Kazuhiro Imamura1, Nozomi Hishikawa, Kenji Ono

  • 1Department of Neurology, Okazaki City Hospital, 3-1 Goshoai, Kouryuuji-cho, 444-8553, Okazaki, Aichi, Japan. katy@syd.odn.ne.jp

Acta Neuropathologica
|December 25, 2004
PubMed

Insights

Dementia in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is linked to activated microglia in the hippocampus. Increased IL-6 and decreased BDNF expression correlate with cognitive decline in these neurodegenerative conditions.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Dementia is a common complication in Parkinson's disease (PD), often occurring late in its progression.
  • Previous research indicated MHC class II-positive microglia in the hippocampus of PD patients may contribute to cognitive decline.

Purpose of the Study:

  • To investigate the distribution of activated microglia and the expression of cytokines and neurotrophic factors in the hippocampus of PD and dementia with Lewy bodies (DLB) patients.
  • To correlate these findings with cognitive function and neuropathological changes.

Main Methods:

  • Immunohistochemistry was used to evaluate microglial activation (MHC class II), alpha-synuclein, and neurotrophic factors (BDNF) in post-mortem brain tissue from PD, DLB, and normal controls (NC).
  • Reverse transcription-PCR (RT-PCR) was employed to assess the mRNA expression of various cytokines (IL-1α, IL-1β, TNF-α, IL-6, TGF-β) and neurotrophic factors (BDNF, GDNF, NGF, NT-3).

Main Results:

  • MHC class II-positive microglia were diffusely distributed in the hippocampus of both PD and DLB brains.
  • Brain-derived neurotrophic factor (BDNF) staining was significantly reduced in the hippocampus of PD and DLB brains compared to normal controls.
  • Interleukin-6 (IL-6) mRNA expression was significantly increased in the hippocampus of PD and DLB brains, while BDNF mRNA was decreased in DLB brains.

Conclusions:

  • The increased presence of activated microglia and elevated IL-6, coupled with reduced BDNF expression in the hippocampus, may underlie the functional neuronal changes and cognitive impairment observed in PD and DLB.
  • These findings highlight the role of neuroinflammation and altered neurotrophic factor signaling in the pathogenesis of dementia associated with these conditions.

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