Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration

Beom Keun Kim, Eun Joo Shin, Hyoung Chun Kim, Yoon Hee Chung, Duy Khanh Dang, Bae Dong Jung, Dae Hun Park, Myung Bok Wie, Won-Ki Kim, Takao Shimizu, Toshitaka Nabeshima, Ji Hoon Jeong

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Platelet-activating factor (PAF), a potent mediator of inflammatory and immune responses, plays various roles in neuronal functions. However, little is known about the role of PAF/platelet-activating factor receptor (PAF-R) in Parkinson's disease. Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) resulted in significant increases in PAF species in the striatum of wild-type mice. These increases paralleled PAF-R gene expression in wild-type mice. Although nuclear factor kappa B (NF-κB) DNA-binding activity was increased significantly in MPTP-treated wild-type mice, this increase was not significant in PAF-R antagonist ginkgolide B (GB)-treated mice or PAF-R knockout (PAF-R-/-) mice. Pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, significantly ameliorated the dopaminergic deficits induced by MPTP in wild-type mice. MPTP treatment significantly increased oxidative damage, the immunoreactivity of ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglial cells, and microglial differentiation of the M1 type in the striatum of wild-type mice. Consistently, PDTC significantly attenuated MPTP-induced behavioral impairments in wild-type mice. However, dopaminergic deficits, oxidative damage, reactive microglial cells, and behavioral impairments induced by MPTP were not significantly observed in GB-treated mice or PAF-R -/- mice. PDTC did not significantly alter the attenuations evident in MPTP-treated PAF-R-/- mice, indicating that NF-κB is a critical target for neurotoxic modulation of PAF-R. We propose for the first time that PAF/PAF-R can mediate dopaminergic degeneration via an NF-κB-dependent signaling process.

Original languageEnglish
Pages (from-to)121-132
Number of pages12
JournalNeurochemistry International
Volume63
Issue number3
DOIs
Publication statusPublished - 2013 Jun 27

Keywords

  • Dopamine
  • Microglia
  • Nuclear factor kappa B
  • Oxidative damage
  • Parkinson's disease
  • Platelet-activating factor receptor
  • Striatum

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    Kim, B. K., Shin, E. J., Kim, H. C., Chung, Y. H., Dang, D. K., Jung, B. D., Park, D. H., Wie, M. B., Kim, W-K., Shimizu, T., Nabeshima, T., & Jeong, J. H. (2013). Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration. Neurochemistry International, 63(3), 121-132. https://doi.org/10.1016/j.neuint.2013.05.010