scholarly journals Hotair and Malat1 Long Noncoding RNAs regulate Bdnf Expression and Oligodendrocyte Precursor Cells Differentiation

2021 ◽  
Author(s):  
Fatemeh khani-Habibabadi ◽  
Leila Zare ◽  
Mohammad Ali Sahraian ◽  
Mohammad Javan ◽  
Mehrdad Behmanesh
Keyword(s):  
Regulatory Mechanism ◽  
Neurodegenerative Disorder ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Bdnf Level ◽  
Bdnf Expression ◽  
Regulatory Processes ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Proper Functions

BDNF has remarkable protective roles in the central nervous system to ensure neurons and glial cell survival and proper functions. The regulatory processes behind the BDNF expression have not been revealed completely. Here, it was explored whether Malat1 and Hotair lncRNAs play roles in the regulation of Bdnf expression level, modification of fingolimod downstream pathway, and oligodendrocytes precursor cells maturation. By Hotair and Malat1 downregulation, their regulatory mechanism on Bdnf expression was investigated. Immunostaining and RT-qPCR assays were employed to assess the effects of fingolimod and lncRNAs on OPCs maturation. The results represented that Hotair and Malat1 lncRNAs may regulate Bdnf expression in primary glial cells significantly, and also can coordinate fingolimod stimulatory effect on Bdnf expression. Furthermore, Malat1 may have a role in the last stages of the intrinsic oligodendrocyte myelination. Here it was demonstrated that these lncRNAs have critical roles in the Bdnf level, fingolimod mechanism of action, and OPCs maturation. Understanding the regulatory mechanism of neurotrophins leads to a better comprehension of the pathogenesis of the neurodegenerative disorder and designing more effective treatments.

scholarly journals Connecting Neuroinflammation and Neurodegeneration in Multiple Sclerosis: Are Oligodendrocyte Precursor Cells a Nexus of Disease?

2021 ◽  
Vol 15 ◽  
Author(s):  
Morgan W. Psenicka ◽  
Brandon C. Smith ◽  
Rachel A. Tinkey ◽  
Jessica L. Williams
Keyword(s):  
Multiple Sclerosis ◽  
Animal Models ◽  
Active Role ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Secreted Factors ◽  
Autoimmune Pathology ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
The Impact

The pathology in neurodegenerative diseases is often accompanied by inflammation. It is well-known that many cells within the central nervous system (CNS) also contribute to ongoing neuroinflammation, which can promote neurodegeneration. Multiple sclerosis (MS) is both an inflammatory and neurodegenerative disease in which there is a complex interplay between resident CNS cells to mediate myelin and axonal damage, and this communication network can vary depending on the subtype and chronicity of disease. Oligodendrocytes, the myelinating cell of the CNS, and their precursors, oligodendrocyte precursor cells (OPCs), are often thought of as the targets of autoimmune pathology during MS and in several animal models of MS; however, there is emerging evidence that OPCs actively contribute to inflammation that directly and indirectly contributes to neurodegeneration. Here we discuss several contributors to MS disease progression starting with lesion pathology and murine models amenable to studying particular aspects of disease. We then review how OPCs themselves can play an active role in promoting neuroinflammation and neurodegeneration, and how other resident CNS cells including microglia, astrocytes, and neurons can impact OPC function. Further, we outline the very complex and pleiotropic role(s) of several inflammatory cytokines and other secreted factors classically described as solely deleterious during MS and its animal models, but in fact, have many neuroprotective functions and promote a return to homeostasis, in part via modulation of OPC function. Finally, since MS affects patients from the onset of disease throughout their lifespan, we discuss the impact of aging on OPC function and CNS recovery. It is becoming clear that OPCs are not simply a bystander during MS progression and uncovering the active roles they play during different stages of disease will help uncover potential new avenues for therapeutic intervention.

scholarly journals Oligodendrocyte Precursor Cells in Spinal Cord Injury: A Review and Update

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Ning Li ◽  
Gilberto K. K. Leung
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Precursor Cells ◽  
High Rate ◽  
Current Evidence ◽  
Oligodendrocyte Precursor Cells ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Demyelinating Disorders

Spinal cord injury (SCI) is a devastating condition to individuals, families, and society. Oligodendrocyte loss and demyelination contribute as major pathological processes of secondary damages after injury. Oligodendrocyte precursor cells (OPCs), a subpopulation that accounts for 5 to 8% of cells within the central nervous system, are potential sources of oligodendrocyte replacement after SCI. OPCs react rapidly to injuries, proliferate at a high rate, and can differentiate into myelinating oligodendrocytes. However, posttraumatic endogenous remyelination is rarely complete, and a better understanding of OPCs’ characteristics and their manipulations is critical to the development of novel therapies. In this review, we summarize known characteristics of OPCs and relevant regulative factors in both health and demyelinating disorders including SCI. More importantly, we highlight current evidence on post-SCI OPCs transplantation as a potential treatment option as well as the impediments against regeneration. Our aim is to shed lights on important knowledge gaps and to provoke thoughts for further researches and the development of therapeutic strategies.

scholarly journals γ–Secretase controls the specification of astrocytes from oligodendrocyte precursor cells via Stat3

2019 ◽  
Author(s):  
Jinxing Hou ◽  
Huiru Bi ◽  
Gang Zou ◽  
Zhuoyang Ye ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Postnatal Development ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Signal Transducer ◽  
Brain Functions ◽  
Mechanistic Analysis ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor

AbstractOligodendrocytes (OLs) and astrocytes play critical roles in a variety of brain functions. OL precursor cells (OPCs) are known to give rise to OLs as well as astrocytes. However, little is known about the mechanism by which OPCs determine their specification choice for OLs versus astrocytes in the central nervous system (CNS). Here we show that genetic inhibition of γ-secretase in OPCs reduces OL differentiation but enhances astrocyte specification. Mechanistic analysis reveals that inhibition of γ-secretase results in decreased levels of Hes1, and that Hes1 down-regulates the expression of signal transducer and activator of transcription3 (Stat3) via binding to specific regions of its promoter. We demonstrate that conditional inactivation of Stat3 in OL lineages restores the number of astrocytes in γ-secretase mutant mice. In summary, this study identifies a key mechanism which controls OPC’s specification choice for OL versus astrocyte during postnatal development. This γ-secretase-dependent machinery may be essential for the CNS to maintain the population balance between OLs and astrocytes.

scholarly journals Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Stefanie Giera ◽  
Rong Luo ◽  
Yanqin Ying ◽  
Sarah D Ackerman ◽  
Sung-Jin Jeong ◽  
...  
Keyword(s):  
Transglutaminase 2 ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Murine Models ◽  
Myelin Formation ◽  
Evolutionarily Conserved ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
G Protein Coupled ◽  
New Strategies

In the central nervous system (CNS), myelin formation and repair are regulated by oligodendrocyte (OL) lineage cells, which sense and integrate signals from their environment, including from other glial cells and the extracellular matrix (ECM). The signaling pathways that coordinate this complex communication, however, remain poorly understood. The adhesion G protein-coupled receptor ADGRG1 (also known as GPR56) is an evolutionarily conserved regulator of OL development in humans, mice, and zebrafish, although its activating ligand for OL lineage cells is unknown. Here, we report that microglia-derived transglutaminase-2 (TG2) signals to ADGRG1 on OL precursor cells (OPCs) in the presence of the ECM protein laminin and that TG2/laminin-dependent activation of ADGRG1 promotes OPC proliferation. Signaling by TG2/laminin to ADGRG1 on OPCs additionally improves remyelination in two murine models of demyelination. These findings identify a novel glia-to-glia signaling pathway that promotes myelin formation and repair, and suggest new strategies to enhance remyelination.

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