NEUROSCIENCE LETTERS
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2021
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IF 3.046
Hui Tian,Yahong Cheng,Yiyuan Zhang,Xinying Bai,Yuan Jiang,Jinjin Li,Shiqi Fan,Hong Ding
This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
研究领域:
神经科学
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药理学
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免疫学
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DOI
高影响因子
Neuroscience Bulletin
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2025
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IF 5.8
An Zihui,Yan Shuo,Wang Jiayi,Qiu Hanqing,Xie Binghua,Feng Shumei,Qiu Mengsheng,Tan Zhou
Myelin is an essential structure that facilitates rapid saltatory conduction in the nervous system. Discrepancies in myelin microstructure are a hallmark of numerous neurological disorders, rendering the assessment of myelin integrity and content an indispensable tool in clinical diagnostics and neuroscience research. Extensive research has been dedicated to scrutinizing its biochemical makeup and morphology under normal, pathological, and experimental conditions over the years. In this review, we present an updated summary of the myelin sheath's structure, composition, and developmental trajectory. We systematically enumerate and contrast eight prevalent myelin staining techniques across dimensions of sensitivity, specificity, and resolution, delving into their underlying staining principles. With an initial application of myelin histology on the mouse demyelination model, our review accentuates the accurate delineation of myelination and the microstructural analysis of the myelin sheath. Such insights are anticipated to significantly contribute to the evaluation and understanding of white matter pathologies.
研究领域:
神经科学
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组织学
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神经病学
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病理学
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生物医学研究
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
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2019
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IF 2.679
Xiao-Yu Zhu,Sheng-Ya Guo,Bo Xia,Chun-Qi Li,Lei Wang,Yong-Hui Wang
RAR-related orphan receptor-γt (RORγt) directs differentiation of proinflammatory T helper 17 cells and is a potential therapeutic target for chronic autoimmune and inflammatory diseases including multiple sclerosis . In this study, zebrafish at days post fertilization treated with ethidium bromide (EB) at a concentration of 75 μM for 72 h were determined as the optimum conditions for the demyelination model development. Zebrafish motility was recorded automatically using a video-track motion detector and quantitative myelin assay was measured by FluoroMyelin staining. A well-known remyelination agent thyroxine (T4) was tested to confirm whether EB-induced motility and myelin damage could be rescued. Two RORγt lead inhibitors GSK805 and SR1001 were assessed for their therapeutic effects on remyelination, axon regeneration, motor neuron promotion and anti-inflammation. T4 significantly improved EB-induced motility dysfunction and myelin damage and promoted myelin basic protein (MBP) regeneration in the demyelinated zebrafish. GSK805 and SR1001 enhanced remyelination in a dose-dependent manner and promoted MBP regeneration. Both GSK805 and SR1001 markedly recovered EB-induced axon and motor neuron damage, and exhibited significantly inhibitory effects of neutrophil infiltration and macrophage recruitment. These results indicate that EB treatment can induce zebrafish demyelination; and the zebrafish demyelination model in combination with quantitative motility and myelin assays is a predictive, reproducible and relatively high throughput screening for rapidly in vivo identification of remyelination compounds and RORγt inhibitors.
研究领域:
神经科学
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2017
·Vol. 16
·期 2
·1864-1870
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IF 1.692
Chao Weng,Man Ding,Shanghua Fan,Qian Cao,Zuneng Lu
Transcription factor 7 like 2 (TCF7L2, also termed TCF4), is a Wnt effector induced transiently in the oligodendroglial lineage. The current well accepted hypothesis is that TCF7L2 inhibits oligodendrocyte differentiation and remyelination through canonical Wnt/β‑catenin signaling. However, recent studies indicated that TCF7L2 activity is required during oligodendrocyte differentiation and remyelination. In order to clarify this, in situ hybridization, immunofluorescence and western blot analysis using in vivo TCF7L2 conditional knockout mice, were performed and it was found that TCF7L2 promotes oligodendrocyte differentiation during myelin formation and remyelination. Furthermore, it was established that TCF7L2 does not affect oligodendrocyte precursor cells during remyelination. These data are of important clinical significance to develop novel therapeutic targets to overcome multiple sclerosis and other demyelinating diseases.
研究领域:
神经科学
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分子生物学
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细胞生物学
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神经病学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2016
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IF 2.371
Zhijian Zhang,Zhengnan Li,Wenwen Deng,Qinghua He,Qiang Wang,Wentao Shi,Qian Chen,Wenjing Yang,Myron Spector,Aihua Gong,Jiangnan Yu,Ximing Xu
Many neurological diseases are closely associated with demyelination caused by pathological changes of oligodendrocytes . Although intrinsic remyelination occurs after injury, the regeneration efficiency of myelinating oligodendrocytes remains to be improved. Herein, we reported an initiative finding of employing a valuable cell source, namely neural crest-derived ectoderm mesenchymal stem cells (EMSCs), for promoting oligodendrocyte differentiation and maturation by co-culturing oligodendrocyte precursor cells (OPCs) with the EMSCs. The results demonstrated that the OPCs/EMSCs co-culture could remarkably increase the number and length of oligodendrocyte processes in comparison with the mono-cultured OPCs and non-contact OPCs/EMSCs transwell culture. Furthermore, the inhibition experiments revealed that the EMSCs-produced soluble factor Sonic hedgehog, gap junction protein connexin 43 and extracellular matrix molecule laminin accounted for the promoted OPC differentiation since inhibiting the function of anyone of the three proteins led to substantial retraction of processes and detachment of oligodendrocytes. Altogether, OPCs/EMSCs co-culture system could be a paradigmatic approach for promoting differentiation and maturation of oligodendrocytes, and EMSCs will be a promising cell source for the treatment of neurological diseases caused by oligodendrocyte death and demyelination.
研究领域:
神经科学
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干细胞生物学
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细胞神经科学
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分子生物学
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DOI
PubMed
高影响因子
EBioMedicine
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2022
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IF 11.205
Xiaoqi Hong,Yujin Jian,Shenghao Ding,Jianpo Zhou,Xiaoli Zheng,Huimin Zhang,Butian Zhou,Canbin Zhuang,Jieqing Wan,Xiaoping Tong
Summary Background Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies. Methods We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke. Findings In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests. Interpretation Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke. Funding This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China ( 82271466 , 82171279 , 31970904 and 31571063 ), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning ( 1510000084 ), Shanghai Pujiang Talent Award ( 15PJ1404600 ), Shanghai Municipal Science and Technology Major Project ( 2018SHZDZX05 ) and Shanghai Science and Technology Project ( 17411954000 ).
研究领域:
神经科学
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药理学
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分子生物学
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临床医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Wu Wensi,Zhang Xiaojun,Zhou Jiaxin,Yang Hongmei,Chen Junjun,Zhao Le,Zhong Junying,Lin Wei-jye,Wang Zhi
Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.
研究领域:
神经科学
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药理学
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老年医学
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分子生物学
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DOI
PubMed
高影响因子
Neural Regeneration Research
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2022
·Vol. 18
·期 7
·1591
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IF 6.058
Liu Yu-Tian,Xu Zhao,Liu Wei,Ren Sen,Xiong He-Wei,Jiang Tao,Chen Jing,Kang Yu,Li Qian-Yun,Wu Zi-Han,Machens Hans-GüNther,Yang Xiao-Fan,Chen Zhen-Bing
Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy . However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy . Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ_0002538 /miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy .
研究领域:
神经科学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2023
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IF 6.1
Dekun Cheng,Zhangtie Wang,Xin Guo,Yiwen Guo,Yu Zhang,Yuanhui Zhao,Ruijie Liu,Ming Chang
Dietary nutritional support for special populations is an effective and feasible method to improve quality of life of patients and reduce medical pressure. The effects of ATSO on chemotherapy population were evaluated by a zebrafish model of demyelination. The results showed that 100 μg/mL ATSO reversed tail morphology damage, axon degeneration, touch response delay, ROS level upregulation and the expression of myelin basic protein decrease in chemotherapy-induced zebrafish. In addition, the expression of myelin markers (including sox10, krox20, pmp22) in oxaliplatin-induced cells was markedly reversed by ATSO and its active components (gondoic acid, erucic acid, nervonic acid). ATSO and its active components could reverse demyelination by ameliorating mitochondrial dysfunction. Conversely, linoleic acid and linolenic acid promoted demyelination by exacerbating mitochondrial dysfunction. Moreover, the Pink1/Parkin pathway was recognized as the main reason for ATSO and its active components to improve mitochondrial function by activating mitophagy and restoring autophagic flow. Taken together, this study demonstrated that ATSO and its active components could be further developed as novel functional food ingredients to antagonize demyelination.
研究领域:
神经科学
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药理学
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营养学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Qingqing Lv,Aolin Yang,Ziyu Han,Ruirui Yu,Junying Zhu,Zhan Shi,Chenggang Yang,Shimiao Dai,Mengru Hao,Yuqing Chen,Ji-Chang Zhou
Low selenium levels are closely associated with reduced cognitive performance and lipid dysregulation, yet the mechanism of action remains unclear. The physiological function of selenium is primarily mediated by selenoproteins. Selenoprotein H (SELENOH), as one of the selenium-containing proteins, has an unelucidated role in regulating cognitive status and lipid metabolism. In this study, we established a Selenoh gene knockout (HKO) mouse model to investigate whether Selenoh mediates the impact of selenium on cognitive function. We found that HKO mice showed a significant decline in cognition compared with the wild-type (HWT) littermates, and were not affected by deficient or excessive selenium, while no differences in anxiety and depression behavior were observed. HKO mice showed reduced myelin basic protein expression in hippocampal oligodendrocytes, with decreased glycolipid levels and increased phospholipid and sphingolipid levels in the hippocampus. Furthermore, the high-fat diet (HFD) exerted no effect on cognition and limited impact on the gene profile in the hippocampus of HKO mice. Compared with those of HWT mice, the myelination pathways in the hippocampus of HKO mice were downregulated as revealed by RNA-seq, which was further confirmed by the reduced expression levels of myelin-related proteins. Finally, HKO increased the expression of hippocampal fatty acid transporter (FATP) 4, and HFD increased the FATP4 expression in HWT mice but not in HKO mice. In summary, our study demonstrated that HKO induced cognitive decline by impairing myelination in oligodendrocytes with disrupted hippocampal lipid metabolism, which provided a novel viewpoint on the selenoprotein-mediated neurodegenerative diseases of selenium.
研究领域:
神经科学
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营养学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Chencong Liu,Yuanyuan Wang,Shitao Shi,Yubo Zheng,Zewei Ye,Jiaqi Liao,Qingfeng Sun,Baokang Dang,Xiaoping Shen
Significant advancements in hydrogel-based epidermal electrodes have been made in recent years. However, inherent limitations, such as adaptability, adhesion, and conductivity, have presented challenges, thereby limiting the sensitivity, signal-to-noise ratio (SNR), and stability of the physiological-electrode interface. In this study, we propose the concept of myelin sheath-inspired hydrogel epidermal electronics by incorporating numerous interpenetrating core–sheath-structured conductive nanofibers within a physically cross-linked polyelectrolyte network. Poly(3,4-ethylenedioxythiophene)-coated sulfonated cellulose nanofibers (PEDOT:SCNFs) are synthesized through a simple solvent-catalyzed sulfonation process, followed by oxidative self-polymerization and ionic liquid (IL) shielding steps, achieving a low electrochemical impedance of 42 Ω. The physical associations within the composite hydrogel network include complexation, electrostatic forces, hydrogen bonding, π–π stacking, hydrophobic interaction, and weak entanglements. These properties confer the hydrogel with high stretchability (770%), superconformability, self-adhesion (28 kPa on pigskin), and self-healing capabilities. By simulating the saltatory propagation effect of the nodes of Ranvier in the nervous system, the biomimetic hydrogel establishes high-fidelity epidermal electronic interfaces, offering benefits such as low interfacial contact impedance, significantly increased SNR (30 dB), as well as large-scale sensor array integration. The advanced biomimetic hydrogel holds tremendous potential for applications in electronic skin (e-skin), human-machine interfaces (HMIs), and healthcare assessment devices.
研究领域:
生物医学工程
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材料科学
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生理监测
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Shuqin Xu,Xiaoli Tang,Maosen Wang,Zhuqun Wang,Rui Zhan,Jinghua Chen
Myelination is modulated by neuron-glial communication, which is an essential physiological process during nerve regeneration. However, available scaffold for myelination of oriented axons is still challenging and lack of sufficient attention in neural tissue engineering. Here, we fabricate an extracellular matrix-mimic hydrogel (GB-SH), which was composed of cellulose nanocrystal grafted with sulfated hyperbranched polyglycerols (SHC) and 3-aminophenylboronic acid modified GelMA (GMPB) for stimuli-responsive release of sodium Danshensu (DSS). SHC with a “lubricative coating” maintained the crystalline core with a uniform size and 17.27 % of sulfation degree. GMPB having a grafting ratio of 14.94 % displayed a glucose-responsive release of dye. GB-SH hydrogels displaying oriented microchannels with controllable pore sizes were constructed by combining directional freeze-casting and photo-crosslinking strategies, which performed improved strengths, high water contents and slow degradation. It also exhibited stimulus (glucose, pH, H 2 O 2 ) triggered release of DSS. In vitro studies revealed that DSS loaded GB-SH enhanced the cellular viability, proliferation and orientation on fibroblast and oligodendrocyte precursor cells (OPCs). This scaffold induced OPCs differentiated into matured oligodendrocytes, which myelinated the extensive axons of hippocampal neurons successfully. The multi-functional hydrogel is a promising platform for studying myelination in vitro and a potential neural transplant in treating traumatic nerve injury.
研究领域:
神经组织工程
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）