Exosome-shuttled MYCBPAP from bone marrow mesenchymal stem cells regulates synaptic remodeling and ameliorates ischemic stroke in rats

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of chemical neuroanatomy Pub Date : 2023-10-01 DOI:10.1016/j.jchemneu.2023.102309
Qiuyue Yan, Yong Yin, Xuechun Li, Meng Li
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Abstract

Background and purpose

Mesenchymal stem cells (MSC) have been demonstrated to improve cardiac function via the secretion of paracrine factors rather than direct differentiation. We, therefore, investigated whether bone marrow-derived MSC (BMSC)-released exosomes (BMSC-exo) enhance neurological recovery in spontaneously hypertensive rats (SHR) with ischemic stroke.

Methods

Markers of BMSC and BMSC-exo were detected to characterize BMSC and BMSC-exo. A green fluorescent PKH-67-labeled assay was conducted to ensure BMSC-exo internalization. Rat neuronal cells (RNC) were induced with Ang II and oxygen-glucose deprivation. The protective effects of BMSC-exo on RNC were studied by CCK-8, LDH, and immunofluorescence assays. SHR were subjected to middle cerebral artery occlusion, and the systolic and diastolic blood pressure changes in the modeled rats were measured. The effects of BMSC-exo on SHR were investigated by mNSS scoring, foot-fault tests, immunohistochemistry, Western blot, TTC staining, TUNEL, and HE staining. The hub genes related to SHR and proteins shuttled by BMSC-exo were intersected to obtain a possible candidate, followed by rescue experiments.

Results

BMSC-exo significantly promoted RNC viability and repressed cell apoptosis and cytotoxicity. Moreover, SHR administrated with BMSC-exo exhibited significant improvement in functional recovery and narrowed infarct size. BMSC-exo shuttled the MYCBPAP protein. Knockdown of MYCBPAP inhibited the protective effects of BMSC-exo on RNC and exacerbated synaptic damage in SHR.

Conclusions

MYCBPAP shuttled by BMSC-exo facilitates synaptic remodeling in SHR, which may contribute to a therapeutic strategy for ischemic stroke treatment.

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骨髓间充质干细胞外泌体介导的MYCBPAP调节突触重塑并改善大鼠缺血性卒中
背景和目的间充质干细胞(MSC)已被证明通过分泌旁分泌因子而不是直接分化来改善心脏功能。因此,我们研究了骨髓源性MSC(BMSC)释放的外泌体(BMSC-exo)是否能增强缺血性中风自发性高血压大鼠(SHR)的神经恢复。方法检测BMSC和BMSC-exo标记,对BMSC和外显子进行鉴定。进行绿色荧光PKH-67标记的测定以确保BMSC外显内化。用Ang II和氧-葡萄糖剥夺诱导大鼠神经细胞(RNC)。通过CCK-8、LDH和免疫荧光法研究BMSC-exo对RNC的保护作用。SHR大脑中动脉闭塞,测量模型大鼠的收缩压和舒张压变化。通过mNSS评分、足部缺损试验、免疫组织化学、蛋白质印迹、TTC染色、TUNEL和HE染色研究BMSC-exo对SHR的影响。将与SHR相关的枢纽基因和BMSC exo穿梭的蛋白质进行交叉,以获得可能的候选基因,然后进行拯救实验。结果BMSC-exo能显著提高RNC的活力,抑制细胞凋亡和细胞毒性。此外,给予BMSC-exo的SHR在功能恢复和缩小梗死面积方面表现出显著改善。BMSC exo穿梭MYCBPAP蛋白。MYCBPAP的敲除抑制了BMSC-exo对SHR RNC的保护作用,并加剧了突触损伤。结论BMSC-exo介导的sMYCBPAP促进SHR突触重构,可能为缺血性脑卒中的治疗策略提供依据。
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来源期刊
Journal of chemical neuroanatomy
Journal of chemical neuroanatomy 医学-神经科学
CiteScore
4.50
自引率
3.60%
发文量
87
审稿时长
62 days
期刊介绍: The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
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