[Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice
[Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice
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DOI：
10.1016/j.neuroscience.2012.11.019
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发表时间：
2013-02
期刊：
影响因子：
3.3
通讯作者：
Tao Wang;Lu Zhang;Mingyang Zhang;Mingyang Zhang;Haijun Bao;W. Liu;Yaoqi Wang;Long Wang;D. Dai;Pan Chang;W. Dong;Xi-ping Chen;Luyang Tao
中科院分区：
文献类型：
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作者：
Tao Wang;Lu Zhang;Mingyang Zhang;Mingyang Zhang;Haijun Bao;W. Liu;Yaoqi Wang;Long Wang;D. Dai;Pan Chang;W. Dong;Xi-ping Chen;Luyang Tao
Humanin（HN）是一种抑制AD相关神经细胞死亡的内源性多肽。HNG是HN的第14位氨基酸丝氨酸被甘氨酸取代的变体，可减少梗死体积，改善缺血/再灌注损伤后的神经功能缺损。在这项研究中，我们的目的是检查HNG对小鼠创伤性脑损伤（TBI）的神经保护作用，并探讨这种保护作用是否与调节细胞凋亡和自噬有关。与溶剂处理组相比，在TBI之前侧脑室（icv）给予HNG的小鼠在损伤的皮层和海马中具有质膜通透性的细胞减少（48 h，P< 0.01），脑损伤体积减小（14和28天，P< 0.05），改善运动性能在TBI后第1-4天（第1-4天，P< 0.05）和在Morris水迷宫测试中的表现改善（第11-13天，P< 0.05）。即使在TBI后1h和2 h腹腔内（ip）给予HNG，也观察到损伤体积减小（第14天，P< 0.05），并且还观察到运动和Morris水迷宫测试缺陷的轻微改善。免疫印迹结果显示，HNG预处理（icv）逆转了TBI诱导的半胱氨酸天冬氨酸特异性蛋白酶-3和聚腺苷二磷酸聚合酶的切割以及Bcl-2的下降，抑制了LC 3 II，Beclin-1和空泡分选蛋白34的活化，并维持了TBI后损伤皮层和海马中p62的水平（与溶剂相比）。总之，HNG治疗改善了小鼠TBI后的形态和功能结果，HNG对TBI的保护作用可能与下调细胞凋亡和自噬有关。
Humanin (HN) has been identified as an endogenous peptide that inhibited AD-relevant neuronal cell death. HNG, a variant of HN in which the 14th amino acid serine was replaced with glycine, can reduce infarct volume and improve neurological deficits after ischemia/reperfusion injury. In this study, we aimed to examine the neuroprotective effect of HNG on traumatic brain injury (TBI) in mice and explored whether the protective effect was associated with regulating apoptosis and autophagy. Compared to vehicle-treated groups, mice administered HNG intracerebroventricularly (icv) prior to TBI had decreased cells with plasmalemma permeability in the injured cortex and hippocampus (48 h, P< 0.01), reduced brain lesion volume (days 14 and 28, P< 0.05), improved motor performance (days 1-4, P< 0.05) and ameliorated performance in the Morris water maze test (days 11-13, P< 0.05) post TBI. Reduced lesion volume (day 14, P< 0.05) was also observed even when HNG was administered intraperitoneally (ip) at 1h and 2h post TBI, and minor amelioration in motor and Morris water maze test deficits was also observed. Immunoblotting results showed that HNG pretreatment (icv) reversed TBI-induced cleavage of cysteinyl aspartate-specific protease-3 and poly ADPribose-polymerase and decline of Bcl-2, suppressed LC3II, Beclin-1 and vacuolar sorting protein 34 activation and maintained p62 levels in the injured cortex and hippocampus post TBI (compared with vehicle). In conclusion, HNG treatment improved morphological and functional outcomes after TBI in mice and the protective effect of HNG against TBI may be associated with down-regulating apoptosis and autophagy.