Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

被引:27
作者
Bok, Eugene [1 ]
Cho, Eun Ju [2 ]
Chung, Eun Sook [2 ]
Shin, Won-Ho [1 ]
Jin, Byung Kwan [2 ]
机构
[1] Korea Inst Toxicol, Dept Predict Toxicol, Daejeon 34114, South Korea
[2] Kyung Hee Univ, Dept Biochem & Mol Biol, Sch Med, Seoul 02447, South Korea
基金
新加坡国家研究基金会;
关键词
Interleukin-4; Parkinson disease; Substantia nigra; Dopaminergic neurons; Lipopolysaccharides; BLOOD-BRAIN-BARRIER; OXIDATIVE STRESS CONTRIBUTES; PARKINSONS-DISEASE; INDUCED NEURODEGENERATION; MICROGLIAL ACTIVATION; HIPPOCAMPAL-NEURONS; NADPH OXIDASE; MODEL; EXPRESSION; RECEPTOR;
D O I
10.5607/en.2018.27.4.309
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The present study investigated the effects of interleukin (IL)-4 on dopamine (DA) neurons in the substantia nigra (SN) in vivo of lipopolysaccharide (LPS)-treated rat. Tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral DA neurons at 3 and 7 day post-LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 day and remained elevated at 7 day post-LPS. IL-4 immunoreactivity was detected exclusively in microglia. IL-4 neutralizing antibody (NA) significantly increased survival of DA neurons in LPS-treated SN in vivo by inhibiting microglial activation and production of proinflammatory mediator such as IL-1 beta as assessed by immunihistochemical, RT-PCR and ELISA analysis, respectively. Accompanying neuroprotection are IL-4NA effects on decreased disruption of blood-brain barrier and astrocytes. The present data suggest that endogenously expressed IL-4 from reactive microglia may be involved in the neuropathological processes of degeneration of DA neurons occurring in Parkinson's disease.
引用
收藏
页码:309 / 319
页数:11
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