以非侵入性方式在脑实质中过表达 miR-132 改善组织修复并解除脑外伤后的记忆损伤

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Meng Jia, Xi Guo, Ru Liu, Lei Sun, Qun Wang, Jianping Wu
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引用次数: 0

摘要

创伤性脑损伤(TBI)是全球严重的公共卫生问题,可导致极高比例的死亡和残疾。目前的治疗策略主要集中于神经元的保护和重建,其中外源性神经干细胞(NSC)移植一直被认为是最有效的治疗方法。然而,由于继发性创伤、移植排斥和脑恶性肿瘤发病率的增加,一种能增强内源性神经发生的非侵入性疗法更适合于创伤性脑损伤的治疗。我们之前的研究表明,miR-132 的过表达可以改善 NSCs 在体外和体内的神经元分化。因此,我们设计了一种名为AAV-PHP.eB的新型AAV载体,通过静脉注射转染脑实质,在TBI后的大脑中过表达miR-132。我们发现,miR-132的过表达可以减少撞击体积,促进齿状回(DG)的神经发生,加速神经母细胞向撞击皮层迁移,改善小胶质细胞介导的炎症反应,并最终恢复学习记忆功能。我们的研究结果表明,基于AAV-PHP.eB的miR-132过表达可以改善内源性组织修复,缓解脑外伤后的临床症状。这项工作将为创伤性脑损伤治疗和其他以明显神经元缺失和记忆损伤为特征的神经系统疾病提供一种新的治疗策略。可控的皮质撞击会引起严重的皮质损伤,并在皮质和海马中积累小胶质细胞。miR-132 的过表达可加速神经母细胞向损伤核心迁移,减少小胶质细胞在同侧皮层和海马的聚集。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Overexpress miR-132 in the Brain Parenchyma by a Non-invasive Way Improves Tissue Repairment and Releases Memory Impairment After Traumatic Brain Injury

Overexpress miR-132 in the Brain Parenchyma by a Non-invasive Way Improves Tissue Repairment and Releases Memory Impairment After Traumatic Brain Injury

Traumatic brain injury (TBI) is a serious public health problem worldwide, which could lead to an extremely high percentage of mortality and disability. Current treatment strategies mainly concentrate on neuronal protection and reconstruction, among them, exogenous neural stem cell (NSC) transplantation has long been regarded as the most effective curative treatment. However, due to secondary trauma, transplant rejection, and increased incidence of brain malignant tumor, a non-invasive therapy that enhanced endogenous neurogenesis was more suitable for TBI treatment. Our previous work has shown that miR-132 overexpression could improve neuronal differentiation of NSCs in vitro and in vivo. So, we engineered a new kind of AAV vector named AAV-PHP.eB which can transfect brain parenchyma through intravenous injection to overexpress miR-132 in brain after TBI. We found that miR-132 overexpression could reduce impact volume, promote neurogenesis in the dentate gyrus (DG), accelerate neuroblast migrating into the impact cortex, ameliorate microglia-mediated inflammatory reaction, and ultimately restore learning memory function. Our results revealed that AAV-PHP.eB-based miR-132 overexpression could improve endogenous tissue repairment and release clinical symptoms after traumatic brain injury. This work would provide a new therapeutic strategy for TBI treatment and other neurological disorders characterized by markable neuronal loss and memory impairment.

Graphical Abstract

miR-132 overexpression accelerates endogenous neurogenesis and releases TBI-induced tissue repairment and memory impairment. Controlled cortical impact onto the cortex would induce serious cortical injury and microglia accumulation in both cortex and hippocampus. Moreover, endogenous neuroblast could migrate around the injury core. miR-132 overexpression could accelerate neuroblast migration toward the injury core and decreased microglia accumulation in the ipsilateral cortex and hippocampus. miR-132 could be a suitable target on neuroprotective therapy after TBI.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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