Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats
Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats
复制标题
鼻内神经生长因子减弱大鼠脑外伤后大脑中 tau 磷酸化。
DOI：
10.1016/j.jns.2014.06.037
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发表时间：
2014-10-15
影响因子：
4.4
通讯作者：
Liu, Xinfeng
中科院分区：
文献类型：
--
作者：
Lv, Qiushi;Lan, Wenya;Liu, Xinfeng
创伤性脑损伤（TBI）是轻度认知障碍和痴呆的重要原因。鼻内给予神经生长因子（NGF）以前已被发现可以改善TBI后的认知功能，但其机制仍不清楚。本研究旨在探讨鼻内注射神经生长因子对创伤性脑损伤后tau蛋白过度磷酸化的影响。使用改良的Feeney重量下降模型来诱导TBI。将大鼠随机分为对照组、TBI组、TBI + NGF组、TBI + PDTC组和TBI + IL-1 ra组。TBI + NGF组大鼠术前给予NGF 5 μ g/d，连续3d。脑外伤后，脑挫伤周围皮质区tau蛋白的过度磷酸化是显著的。免疫印迹和免疫染色结果显示，鼻内预处理的NGF显着降低tau蛋白磷酸化。为了评估潜在的机制，测定了糖原合成酶激酶3 β（GSK-3 β）、白细胞介素-1 β（IL-1 β）的水平和核因子-κ B（NF-κ B）的DNA结合活性。NGF显著抑制GSK-3 β。NGF还降低TBI诱导的IL-1 β和NF-κ B DNA结合活性的升高。此外，注射PDTC和IL-1 ra以证明NF-κ B B、IL-1 β和GSK-3 β之间的潜在信号通路。总之，这些发现表明鼻内NGF可以有效地减轻TBI后tau蛋白的过度磷酸化，这可能涉及与NF-κ B B相关的整合信号通路。(C)2014由Elsevier B. V.出版
Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment and dementia. Intranasal administration of nerve growth factor (NGF) has previously been found to improve cognitive function after TBI, but the mechanism remains unclear. This study aimed to investigate the effects of intranasal NGF on the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model was used to induce TBI. Rats were randomly divided into control group, TBI group, TBI + NGF group, TBI + PDTC group and TBI + IL-1ra group. Rats in TBI + NGF group were administered with NGF (5 mu g/d) for 3 d before surgery. Hyperphosphorylated tau protein was remarkable in the peri-contusional cortex area with TBI. Both western blotting and immunostaining results displayed intranasal pretreatment of NGF significantly reduced tau phosphorylation. To evaluate the underlying mechanism, the levels of glycogen synthase kinase 3 beta (GSK-3 beta), interleukin-1 beta (IL-1 beta), and the DNA binding activity of nuclear factor-kappa B (NF-kappa B) were assayed. NGF markedly inhibited GSK-3 beta. NGF also reduced TBI-induced elevation of IL-1 beta and NF-kappa B DNA binding activity. Furthermore, PDTC and IL-1ra were injected to prove a potential signaling pathway among NF-kappa B, IL-1 beta and GSK-3 beta. Taken together, these findings demonstrated that intranasal NGF could effectively attenuate the hyperphosphorylation of tau after TBI, which might involve an integrated signaling pathway related to NF-kappa B. (C) 2014 Published by Elsevier B.V.