黑质
MAPK/ERK通路
纹状体
MPTP公司
小胶质细胞
多巴胺能
星形胶质细胞
酪氨酸羟化酶
胶质纤维酸性蛋白
神经科学
免疫标记
内分泌学
内科学
化学
生物
多巴胺
医学
细胞生物学
激酶
中枢神经系统
免疫组织化学
炎症
作者
Sumit Sarkar,Edward Lu,James Raymick,Joseph P. Hanig,Qiang Gu
出处
期刊:Current Neurovascular Research
[Bentham Science]
日期:2019-01-18
卷期号:15 (4): 336-344
被引量:9
标识
DOI:10.2174/1567202616666181123152601
摘要
Introduction: Parkinson’s Disease (PD) is a debilitating, age-related disorder characterized by selective degeneration of dopaminergic neurons in the midbrain substantia nigra (SNc). Dopaminergic neurons originating in the midbrain project to the striatum (Caudate-putamen-CPU). Although studies have suggested that the extracellular signal-regulated kinase ½ (ERK ½) in the brain is activated after 1-Methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) exposure, to our knowledge no study has yet been done to demonstrate whether such activation occurs in neurons or in glia. Material and Methods: In the current study, we utilized both an acute and a repeat dose mouse model of PD using the neurotoxicant MPTP as the causative agent. Immunohistochemical studies using phospho ERK ½ antibody suggested that ERK ½ activation takes place in the striatum (CPU) and SNc of both animal models. Moreover, double immunolabeling studies using phospho ERK ½ and the microglial marker, CD11b or the astrocyte marker, Glial Fibrillary Acidic Protein (GFAP) suggested that the phospho ERK ½ was present exclusively in the microglia and not in the astrocytes. Results: Western Blot results suggested that there were no alterations in ERK in either MPTPtreated animals or in control animals; however, phospho ERK ½ was found to be significantly increased in the striatum and SNc in both acute chronic mouse PD models. Tyrosine Hydroxylase (TH) immunolabeling revealed significant decreases in dopaminergic neurons in the SNc in both animal models’ concomitant with activation of microglia and ERK activation. Conclusion: These observations suggest that ERK activation takes place following MPTP treatment and that activation of ERK occurs primarily in the microglia. The data provided also suggest that ERK activation may be involved in transcriptional activation of microglia following neurotoxicant insults. Keywords: ERK, pERK, microglia, Parkinson's Disease, striatum, Alzheimer's Disease (AD).
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