Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: Implications for TDP-43 in the physiological response to neuronal injury
Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: Implications for TDP-43 in the physiological response to neuronal injury
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DOI：
10.1016/j.brainres.2008.10.021
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发表时间：
2009-01-16
期刊：
影响因子：
2.9
通讯作者：
Strong, Michael J.
中科院分区：
文献类型：
--
作者：
Moisse, Katie;Volkening, Kathryn;Strong, Michael J.
我们在成年C57 BL/6小鼠中进行了坐骨神经切断术，并在28天内观察了TDP-43和颗粒蛋白前体（PGRN）的表达模式。TDP-43的表达显着上调轴突切断运动神经元，与突出的胞质免疫反应性成为最大的损伤后7天，并恢复到基线水平损伤后28天。通过蛋白质印迹证实TDP-43表达增加。TDP-43 mRNA表达也增加。这与神经元PGRN表达呈负相关，神经元PGRN表达在第7天明显降低，在损伤后第28天恢复至基线。相反，小胶质细胞PGRN的表达显着增加，并与炎症反应轴突切断。胞质TDP-43与Staufen和TIA-1共定位，分别是RNA转运和应激颗粒的标志物。我们没有观察到TDP-43或PGRN与降解颗粒（P体）或活化的半胱天冬酶3的共定位。这些结果表明，TDP-43的表达在神经元损伤后发生改变，恢复后恢复正常表达。这些发现表明，TDP-43表达的上调与突出的细胞溶质定位在运动神经元损伤的退行性过程，如ALS可能实际上代表了一个适当的响应神经元损伤。(C)2008 Elsevier B. V.保留所有权利。
We have performed sciatic axotomies in adult C57BL/6 mice and observed TDP-43 and progranulin (PGRN) expression patterns over 28 days. TDP-43 expression was markedly upregulated in axotomized motor neurons, with prominent cytosolic immunoreactivity becoming maximal by post-injury day 7 and returning to baseline levels by post-injury day 28. Increased TDP-43 expression was confirmed by western blot. TDP-43 mRNA expression was also increased. This was inversely correlated with neuronal PGRN expression which was clearly reduced by day 7 with a return to baseline by post-injury day 28. In contrast, microglial PGRN expression was dramatically increased, and correlated with the inflammatory response to axotomy. Cytosolic TDP-43 colocalized with Staufen and TIA-1, markers for RNA transport and stress granules respectively. We did not observe colocalization of TDP-43 or PGRN with degradative granules (P-bodies) or activated caspase 3. These results indicate that TDP-43 expression is altered in response to neuronal injury and that normal expression is restored following recovery. These findings suggest that the upregulation of TDP-43 expression with prominent cytosolic localization in motor neurons injured by degenerative processes such as ALS may actually represent an appropriate response to neuronal injury. (C) 2008 Elsevier B.V. All rights reserved.