کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6277908 | 1295777 | 2009 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Axonal ligation induces transient redistribution of TDP-43 in brainstem motor neurons
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کلمات کلیدی
DABLCMTAR DNA binding protein 43TDP-43LC3amyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکamyotrophic lateral sclerosis (ALS) - اسکلروز جانبی جانبی آمیوتروفیک (ALS)ALS - بیماری اسکلروز جانبی آمیوتروفیکaxonal flow - جریان آکسونdiaminobenzidine - دیامینو بنزیدینmicrotubule-associated protein1 light chain 3 - زنجیره سبک پروتئین مرتبط با میکروتوبول 3Hypoglossal nerve - عصب هیپوگلوزالیlaser capture microdissection - لیزر ضبط میکرو دیسکسیونImportin - وارداتChAT - چتCholine acetyltransferase (ChAT) - کراتین استیل ترانسفراز (CHAT)choline acetyltransferase - کولین استیل ترانسفراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Nuclear exclusion of TAR DNA binding protein 43 (TDP-43) and formation of cytosolic aggregates are a pathological characteristic of amyotrophic lateral sclerosis (ALS). However, the molecular basis of the aberrant distribution of TDP-43 remains elusive. Here, we show evidence that axonal ligation induced transient nuclear exclusion and peripheral accumulation of TDP-43, without apparent cytosolic aggregates in hypoglossal neurons in mice. Immunohistochemistry showed marked loss of nuclear TDP-43 7-14 days after ligation, which was accompanied by reduction of choline acetyltransferase (ChAT). TDP-43 staining was restored in the nucleus on day 28 exclusively in the neurons with normalized ChAT expression. We also showed that importin β, which was shown to mediate nuclear transport of TDP-43 was downregulated transiently by nerve ligation. The analysis of the peripheral nerves proximal to the ligation revealed that TDP-43 markedly accumulated with a concomitant decrease in active autophagosome. Moreover, we showed that TDP-43 was present in the microsome fraction containing endoplasmic reticulum (ER) or autophagosomes in the brainstem section, indicating that TDP-43 is axonally transported with vesicles. These results indicate that axonal damage is associated with redistribution of TDP-43 through the combination of defective axonal autophagy periphery and the impaired nuclear transport system in the soma. Moreover, it was also shown that transient redistribution of TDP-43 does not prevent motor neurons from axonal regeneration. Therefore, our data suggest that the subcellular distribution of TDP-43 correlates to the innervation status of motor neurons, which may be governed by unidentified cause of ALS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 164, Issue 4, 29 December 2009, Pages 1565-1578
Journal: Neuroscience - Volume 164, Issue 4, 29 December 2009, Pages 1565-1578
نویسندگان
T. Sato, S. Takeuchi, A. Saito, W. Ding, H. Bamba, H. Matsuura, Y. Hisa, I. Tooyama, M. Urushitani,