Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans.
Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans.
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DOI：
10.1007/s00401-011-0909-9
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发表时间：
2011-12
影响因子：
12.7
通讯作者：
Smith DH
中科院分区：
文献类型：
--
作者：
Johnson VE;Stewart W;Trojanowski JQ;Smith DH
神经交互反应- dna结合蛋白（TDP-43）的病理性磷酸化和亚细胞易位被确定为泛素化包涵体额颞叶变性（FTLD）和肌萎缩性侧索硬化症（ALS）的主要疾病蛋白。最近，TDP-43蛋白病变在重复性创伤性脑损伤（TBI）引起的拳击性痴呆或慢性创伤性脑病中有报道。虽然单次脑外伤与阿尔茨海默病的发展和神经原纤维缠结的频率增加有关，但TDP-43蛋白病变尚未与单次脑外伤后的生存率进行检查。利用免疫组织化学特异性检测病理磷酸化TDP-43 （p-TDP-43）和磷酸化非依赖性TDP-43 (pi-TDP-43)，我们检测了单次TBI的急性（n = 23，生存期< 2周）和长期（n = 39，生存期1-47年）幸存者与年龄匹配的对照组（n = 47）。对海马、内侧颞叶、扣带回、额上回、脑干等多区域进行检查。未发现单一TBI病史与异常磷酸化的TDP-43 （p-TDP-43）内含物之间存在关联。具体来说，62例TBI病例中只有3例显示p-TDP-43病理，而47例对照病例中有2例。然而，尽管急性和长期TBI后p-TDP-43的聚集体没有增加，但在急性和长期TBI后，细胞质中对磷酸化非依赖性TDP-43的免疫反应性普遍增加。此外，虽然单次脑损伤可诱发多种长期神经退行性改变，但TDP-43蛋白病变的缺失可能表明，单次脑损伤诱导的过程与重复性脑损伤诱导的过程存在根本差异。
The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer’s disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43) and phosphorylation-independent TDP-43 (pi-TDP-43), we examined acute (n = 23: Survival < 2 weeks) and long-term (n = 39; 1–47 years survival) survivors of a single TBI versus age-matched controls (n = 47). Multiple regions were examined including the hippocampus, medial temporal lobe, cingulate gyrus, superior frontal gyrus and brainstem. No association was found between a history of single TBI and abnormally phosphorylated TDP-43 (p-TDP-43) inclusions. Specifically, just 3 of 62 TBI cases displayed p-TDP-43 pathology versus 2 of 47 control cases. However, while aggregates of p-TDP-43 were not increased acutely or long-term following TBI, immunoreactivity to phosphorylation-independent TDP-43 was commonly increased in the cytoplasm following TBI with both acute and long-term survival. Moreover, while single TBI can induce multiple long-term neurodegenerative changes, the absence of TDP-43 proteinopathy may indicate a fundamental difference in the processes induced following single TBI from those of repetitive TBI.
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影响因子：
38.1
作者：
Chen-Plotkin, Alice S.;Lee, Virginia M. -Y.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
--
作者：
Geser, Felix;Martinez-Lage, Maria;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
6
作者：
Chen, XH;Siman, R;Smith, DH
通讯作者：
Smith, DH
影响因子：
11
作者：
DALE, GE;LEIGH, PN;ROBERTS, GW
通讯作者：
ROBERTS, GW
影响因子：
12.7
作者：
Arai, Tetsuaki;Mackenzie, Ian R. A.;Akiyama, Haruhiko
通讯作者：
Akiyama, Haruhiko