کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8553322 | 1562584 | 2018 | 28 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
NLRP3 inflammasome activation in the thymus of MPTP-induced Parkinsonian mouse model
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Ample evidence shows that Parkinson's disease (PD) is more than simply a central nervous system (CNS) disorder: the immune system appears to participate in PD pathogenesis. Extracellular misfolded α-synuclein (α-syn) may trigger an inflammatory response in the brain. Abnormal immune responses are involved in the development of PD, but little is known about the relationship between the thymus malfunction and the pathogenesis of PD. The present study investigated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced impairment in thymus and explored possible mechanisms involved in PD pathogenesis. After subcutaneous injection of MPTP (25â¯mg/kg) every 4â¯days for 40-days, immune responses became unbalanced, with increased IL-1β concentrations. On histopathology, mice treated with MPTP displayed pathological involution and damaged ultrastructure of the thymus. Both the PD-related oligomeric α-synuclein and oxidative stress related nitrated-α-synuclein (Tyr125, Tyr133) in mice treated with MPTP were elevated. Correspondingly, oxidative stress damage was detected in the form of increased 8-hydroxyguanosine staining. Moreover, MPTP significantly increased expression of caspase-8, NF-κB, NLPR3, and caspase-1 in the thymus. These results suggested that MPTP was toxic to mouse thymus via a mechanism involving the NF-κB and NLRP3 inflammasome pathway. These results suggested that environmental factors may lead to pathological changes in the thymus that are similar to those in the central nervous system. A disordered thymus might take part in the development of PD, and its enhanced immune response might promote the degenerative changes in the brain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 288, 15 May 2018, Pages 1-8
Journal: Toxicology Letters - Volume 288, 15 May 2018, Pages 1-8
نویسندگان
Lu Wen, Qiu-Shuang Zhang, Yang Heng, Ying Chen, Shuo Wang, Yu-He Yuan, Nai-Hong Chen,