| RRC ID |
21966
|
| 著者 |
Kim BK, Shin EJ, Kim HC, Chung YH, Dang DK, Jung BD, Park DH, Wie MB, Kim WK, Shimizu T, Nabeshima T, Jeong JH.
|
| タイトル |
Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration.
|
| ジャーナル |
Neurochem Int
|
| 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.
|
| 巻・号 |
63(3)
|
| ページ |
121-32
|
| 公開日 |
2013-9-1
|
| DOI |
10.1016/j.neuint.2013.05.010
|
| PII |
S0197-0186(13)00161-7
|
| PMID |
23743065
|
| MeSH |
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
Animals
Corpus Striatum / drug effects
Corpus Striatum / metabolism
Dopaminergic Neurons / drug effects*
Mice
Mice, Knockout
NF-kappa B / metabolism
Platelet Membrane Glycoproteins / genetics
Platelet Membrane Glycoproteins / physiology*
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / physiology*
|
| IF |
3.881
|
| 引用数 |
18
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
NEUROSCIENCES
|
| リソース情報 |
| 実験動物マウス |
RBRC01733 |
