کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6017172 | 1580158 | 2016 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS)
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
CD68AChRGDNFalpha-bungarotoxinα-BTXC9orf72CD11Bcluster of differentiation 11bGAPDHEGTAGFAPGFRα1BVCBupivacaine hydrochlorideEDTA - اتیلن دی آمین تترا استیک اسید ethylene glycol tetraacetic acid - اتیلن گلیکول تتراستیک اسیدEthylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکALS - بیماری اسکلروز جانبی آمیوتروفیکanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاCluster of differentiation 68 - خوشه تمایز 68BBB - سد خونی مغزیGlial cell line-derived neurotrophic factor - فاکتور نوروتروفی مشتق از سلول گلیاییGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالchromosome 9 open reading frame 72 - کروموزوم 9 قاب خواندن باز 72glyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژنازacetylcholine receptor - گیرنده استیل کولین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor dysfunction and loss of large motor neurons in the spinal cord and brain stem. While much research has focused on mechanisms of motor neuron cell death in the spinal cord, degenerative processes in skeletal muscle and neuromuscular junctions (NMJs) are also observed early in disease development. Although recent studies support the potential therapeutic benefits of targeting the skeletal muscle in ALS, relatively little is known about inflammation and glial responses in skeletal muscle and near NMJs, or how these responses contribute to motor neuron survival, neuromuscular innervation, or motor dysfunction in ALS. We recently showed that human mesenchymal stem cells modified to release glial cell line-derived neurotrophic factor (hMSC-GDNF) extend survival and protect NMJs and motor neurons in SOD1G93A rats when delivered to limb muscles. In this study, we evaluate inflammatory and glial responses near NMJs in the limb muscle collected from a rat model of familial ALS (SOD1G93A transgenic rats) during disease progression and following hMSC-GDNF transplantation. Muscle samples were collected from pre-symptomatic, symptomatic, and end-stage animals. A significant increase in the expression of microglial inflammatory markers (CD11b and CD68) occurred in the skeletal muscle of symptomatic and end-stage SOD1G93A rats. Inflammation was confirmed by ELISA for inflammatory cytokines interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in muscle homogenates of SOD1G93A rats. Next, we observed active glial responses in the muscle of SOD1G93A rats, specifically near intramuscular axons and NMJs. Interestingly, strong expression of activated glial markers, glial fibrillary acidic protein (GFAP) and nestin, was observed in the areas adjacent to NMJs. Finally, we determined whether ex vivo trophic factor delivery influences inflammation and terminal Schwann cell (TSC) response during ALS. We found that intramuscular transplantation of hMSC-GDNF tended to exhibit less inflammation and significantly maintained TSC association with NMJs. Understanding cellular responses near NMJs is important to identify suitable cellular and molecular targets for novel treatment of ALS and other neuromuscular diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 277, March 2016, Pages 275-282
Journal: Experimental Neurology - Volume 277, March 2016, Pages 275-282
نویسندگان
Jonathan M. Van Dyke, Ivy M. Smit-Oistad, Corey Macrander, Dan Krakora, Michael G. Meyer, Masatoshi Suzuki,