Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration
- Authors
- Kim, Beom Keun; Shin, Eun-Joo; Kim, Hyoung-Chun; Chung, Yoon Hee; Dang, Duy-Khanh; Jung, Bae-Dong; Park, Dae-Hun; Wie, Myung Bok; Kim, Won-Ki; Shimizu, Takao; Nabeshima, Toshitaka; Jeong, Ji Hoon
- Issue Date
- 9월-2013
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Platelet-activating factor receptor; Parkinson' s disease; Striatum; Dopamine; Nuclear factor kappa B; Microglia; Oxidative damage
- Citation
- NEUROCHEMISTRY INTERNATIONAL, v.63, no.3, pp.121 - 132
- Indexed
- SCIE
SCOPUS
- Journal Title
- NEUROCHEMISTRY INTERNATIONAL
- Volume
- 63
- Number
- 3
- Start Page
- 121
- End Page
- 132
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/102306
- DOI
- 10.1016/j.neuint.2013.05.010
- ISSN
- 0197-0186
- 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 PAP 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-kappa B) 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 (PAP-R-/-) mice. Pyrrolidine dithiocarbamate (PDTC), an NF-kappa B 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 PAP-R-/- mice. PDTC did not significantly alter the attenuations evident in MPTP-treated PAF-R-/- mice, indicating that NF-kappa B 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-kappa B-dependent signaling process. (C) 2013 Elsevier Ltd. All rights reserved.
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