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

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19 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

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