Browsing by Subject "Remyelination"

Now showing 1 - 5 of 5
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    Hedgehog Signaling in CNS Remyelination
    (MDPI, 2022-07-21) Fang, Minxi; Tang, Tao; Qiu, Mengsheng; Xu, Xiaofeng; Anatomy, Cell Biology and Physiology, School of Medicine
    Remyelination is a fundamental repair process in the central nervous system (CNS) that is triggered by demyelinating events. In demyelinating diseases, oligodendrocytes (OLs) are targeted, leading to myelin loss, axonal damage, and severe functional impairment. While spontaneous remyelination often fails in the progression of demyelinating diseases, increased understanding of the mechanisms and identification of targets that regulate myelin regeneration becomes crucial. To date, several signaling pathways have been implicated in the remyelination process, including the Hedgehog (Hh) signaling pathway. This review summarizes the current data concerning the complicated roles of the Hh signaling pathway in the context of remyelination. We will highlight the open issues that have to be clarified prior to bringing molecules targeting the Hh signaling to demyelinating therapy.
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    Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics
    (BMC, 2022-10-26) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
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    Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics
    (Springer, 2022-10-26) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
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    Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after SpinalCord Injury
    (Society for Neuroscience, 2010-02-24) Cao, Qilin; He, Qian; Wang, Yaping; Cheng, Xiaoxin; Howard, Russell M.; Zhang, Yiping; DeVries, William H.; Shields, Christopher B.; Magnuson, David S. K.; Xu, Xiao-Ming; Kim, Dong H.; Whittemore, Scott R.; Neurological Surgery, School of Medicine
    Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs, and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI.
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    Wuzi Yanzong Pill relieves CPZ-induced demyelination by improving the microenvironment in the br
    (Elsevier, 2022-12-10) Li, Yan-Rong; Sun, Meng-Ying; Hang, Wei; Xiao, Qi; Fan, Hui-Jie; Jia, Lu; Jin, Xiao-Ming; Zhang, Bo; Xiao, Bao-Guo; Ma, Cun-Gen; Chai, Zhi; Anatomy, Cell Biology and Physiology, School of Medicine
    Ethnopharmacology relevance: Wuzi Yanzong Pill (WYP), a well-known prescription for invigorating the kidney and essence, which is widely used to treat infertility such as oligoasthenospermia. Studies have shown that WYP can be used to treat neurological diseases, but its therapeutic effects and mechanisms for multiple sclerosis (MS) remain unclear. Aim of the study: Based on the establishment of Cuprizone (CPZ)-induced demyelination model, this study determined the effect of WYP on remyelination by detecting changes in the microenvironment of the central nervous system. Materials and methods: C57BL/6 mice were divided into three groups. The CPZ group and CPZ + WYP group were fed with 0.2% CPZ feed, and the control group was fed normal feed, for 6 weeks. At the end of the second week, the CPZ + WYP group was gavaged with WYP solution (16 g/kg/d), and the other two groups were gavaged with normal saline twice a day with an interval of 12 h each time, for 4 weeks. Forced swimming and elevated plus maze were used to detect changes in anxiety and depression before and after treatment. Luxol fast blue staining and the expression of MBP were used to evaluate the demyelination of the brain. Western blot was used to detect the expression of microglia and their subtype markers Iba-1, Arg-1, iNOS, the expression of neurotrophic factors BDNF, GDNF, CNTF, and the expression of oligodendrocyte precursor cells NG2. ELISA detected the content of IL-6, IL-1β, IL-10, TGF-β, BDNF, GDNF, CNTF in the brain. The distribution of Iba-1 in the corpus callosum was observed by immunofluorescence. Results: The results showed that on the basis of improving mood abnormalities and demyelination, WYP reduced the protein content of Iba-1 and iNOS, increased the protein content of Arg-1, and reduce accumulation of microglia in the corpus callosum. In addition, WYP reduced the secretion of IL-6 and IL-1β while promoting the secretion of IL-10 and TGF-β. After WYP intervention treatment, the levels of neurotrophic factors BDNF, GDNF, CNTF increased. Due to the improvement of inflammatory and nutritional environment in the CNS, promoting the proliferation of NG2 oligodendrocyte, increased the expression of MBP, and repairing myelin sheath. Conclusion: Our results indicated that WYP promoted the proliferation and development of oligodendrocytes by improving the CNS microenvironment, effectively alleviating demyelination.