Recombinant human thioredoxin-1 promotes neurogenesis and facilitates cognitive recovery following cerebral ischemia in mice

NEUROPHARMACOLOGY

卷:77

Article

Tian, Li¹  Nie, Huang¹  Zhang, Yang²  Chen, Yu¹  Peng, Zhengwu³  Cai, Min¹  Wei, Haidong¹  Qin, Pei¹  Dong, Hailong¹  Xiong, Lize¹ 

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Orthoped Surg, Xian 710032, Peoples R China

[3] Fourth Mil Med Univ, Xijing Hosp, Dept Psychosomat Med, Xian 710032, Peoples R China

关键词: Recombinant human Trx-1;    Cerebral ischemia;    Hippocampus;    Neurogenesis;    Learning and memory;    ERIC signaling pathway;   

DOI  :  10.1016/j.neuropharm.2013.10.027

来源: Elsevier

【 摘 要 】

Cerebral ischemia (CI) can induce loss of hippocampal neurons, causing cognitive dysfunction such as learning and memory deficits. In adult mammals, the hippocampal dentate gyrus contains neural stem cells (NSCs) that continuously generate newborn neurons and integrate into the pre-existing networks throughout life, which may ameliorate cognitive dysfunction following CI. Recent studies have demonstrated that recombinant human thioredoxin-1 (rhTrx-1) could promote proliferation of human adipose tissue-derived mesenchymal stem cells and angiogenesis. To investigate whether rhTrx-1 also regulates hippocampal neurogenesis following Cl and its underlying mechanisms, adult mice were subjected to bilateral common carotid arteries occlusion (BCCAO) to induce CI and treated with rhTrx-1 before reperfusion. Mice treated with rhTrx-1 showed shortened escape latencies in Morris water maze by 30 days and improvements in spatial memory demonstrated by probe trial test. Enhanced NSCs proliferation was observed at day 14, indicated by BrdU and Ki67 immunostaining. Doublecortin (DCX)(+) cells were also significantly increased following rhTrx-1 treatment. Despite increases in BrdU(+)/NeuN(+) cells by day 30, the double-labeling to total BrdU(+) ratio was not affected by rhTrx-1 treatment. The promotive effects of rhTrx-1 on NSCs proliferation and differentiation were further confirmed in in vitro assays. Western blot revealed increased ERK1/2 phosphorylation after rhTrx-1 treatment, and the ERK inhibitor 130126 abrogated the effects of rhTrx-1 on NSCs proliferation. These results provide initial evidence that rhTrx-1 effects neurogenesis through the ERIC signaling pathway and are beneficial for improving spatial learning and memory in adult mice following global CI. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

【 授权许可】

Free