Accelerated Dystrophy and Decay of Oligodendrocyte Precursor Cells in the APP/PS1 Model of Alzheimer’s-Like Pathology

AbstractMyelin disruption is a feature of natural aging and of Alzheimer’s disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Here, we examined age-related changes in OPCs in APP/PS1 mice, a model for AD-like pathology, compared with non-transgenic (Tg) age-matched controls. Analysis was performed in the CA1 area of the hippocampus following immunolabelling for NG2 with the nuclear dye Hoescht, to identify OPC and OPC sister cells, a measure of OPC replication, together with Gpr17 and Olig2 for oligodendrocytes and myelin basic protein (MBP) immunostaining as a measure of myelination. The results indicate a decrease in the number of OPCs between 9 and 14 months in natural ageing and this occurred earlier at 9 months in APP/PS1 mice, without further decline at 14 months. The number of OPC sister cells was unaltered in natural aging, but declined significantly at 14-months in APP/PS1 mice. The number of GPR17+ and Olig2+ oligodendrocytes was not altered in APP/PS1, whereas MBP immunostaining increased between 9 and 14 months in natural ageing, but not in APP/PS1 mice. Notably, OPCs displayed marked morphological changes at 14 months in APP/PS1 mice, characterized by an overall shrinkage of OPC process domains and increased process branching, characteristic of reactive pathological changes. The results indicate that OPC and myelin disruption are pathological signs in the APP/PS1 mouse model of AD.

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Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

10.21203/rs.3.rs-103731/v1 ◽

2020 ◽

Author(s):

Lu Jiang ◽

Xiaoyan Zhang ◽

Dan Xu ◽

Wenjin Zhang ◽

GuoGuang Peng ◽

...

Keyword(s):

Direct Contact ◽

Neurological Diseases ◽

The Elderly ◽

Oligodendrocyte Progenitor Cells ◽

Oligodendrocyte Precursor Cells ◽

Nanoparticle Tracking Analysis ◽

Gap Junction Channel ◽

Proliferation And Differentiation ◽

Sirna Interference ◽

Oligodendrocyte Precursor

Abstract Background: Neurodegenerative diseases, caused by the loss of neurons or myelin sheath, are some of the most important neurological diseases that threaten the health of the elderly. In the CNS, oligodendrocytes (OLs) are the only cells that can form myelin. Astrocytes (ASTs) play a generally beneficial role in remyelination, including the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) to OLs. However, the specific downstream mechanism is unclear.Methods: This study investigated the proliferation of OPCs in OPCs mono-culture, OPCs culture with ASTs supernatant, and ASTs-OPCs co-culture. Gene Ontology (GO) analysis were used to analyze the differentially expressed genes after transcriptome sequencing of these OPCs. Electron microscope, Nanoparticle Tracking Analysis (NTA), Fluorescence tracing of exosomes and Western blot were used to evaluate the effects of exsomes. Pull-down, co-immunoprecipitation (Co-IP) and mass spectrometry analys were conducted to find the downstream signal proliferation which is transmitted information into OPCs.Reasults: Direct contact co-culture of ASTs and OPCs promotes the proliferation of OPCs. After Cx47 siRNA interference under ASTs-OPCs co-culture, Chi3l1 secretion in exosome reveals associated decrease, and OPCs proliferation decreased. The cell proliferation induced by Chi3l1 was inhibited after siRNA interfered with Myh9, and the expression of cyclin D1 was also decreased.Conclusions: These results suggest that ASTs transmit information to OPCs by increasing gap junction channel Cx47, thereby promoting the secretion of Chi3l1 in exosome of OPCs. The secretory form of Chi3l1 in exosome might be easier to enter the target cell than in extracellular supernatant, which is beneficial to the activation of Myh9 to promote OPCs proliferation. This may be a potential target for drugs rescuing neurodegeneration diseases related to remyelination.

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Can oligodendrocyte precursor cells be a therapeutic target for mitigating cognitive decline in cerebrovascular disease?

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20929432 ◽

2020 ◽

Vol 40 (8) ◽

pp. 1735-1736 ◽

Cited By ~ 2

Author(s):

Ken Arai

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Memory Deficits ◽

Vascular Cognitive Impairment ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Age Related ◽

White Matter Development ◽

Oligodendrocyte Precursor ◽

Novel Therapeutic

Oligodendrocyte precursor cells (OPCs) give rise to mature myelin-forming oligodendrocytes during white matter development. In adult brains, some populations of OPCs remain to renew oligodendrocyte pools and myelin. Two recent studies highlight the importance of OPCs in white matter homeostasis. Genetic tracing studies suggest that age-related decline in OPCs may contribute to diminished myelin renewal and memory deficits in mouse models. Single cell transcriptomics and imaging may now define specific subsets of OPCs involved in process elaboration, motility and myelination. These advances raise the possibility of pursuing OPCs as novel therapeutic targets for vascular cognitive impairment.

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Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in Exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

10.21203/rs.3.rs-108120/v1 ◽

2020 ◽

Author(s):

Lu Jiang ◽

XIAOYAN ZHANG ◽

Dan Xu ◽

Wenjin Zhang ◽

GuoGuang Peng ◽

...

Keyword(s):

Direct Contact ◽

Neurological Diseases ◽

The Elderly ◽

Oligodendrocyte Progenitor Cells ◽

Oligodendrocyte Precursor Cells ◽

Nanoparticle Tracking Analysis ◽

Gap Junction Channel ◽

Proliferation And Differentiation ◽

Sirna Interference ◽

Oligodendrocyte Precursor

Abstract Background: Neurodegenerative diseases, caused by the loss of neurons or myelin sheath, are some of the most important neurological diseases that threaten the health of the elderly. In the CNS, oligodendrocytes (OLs) are the only cells that can form myelin. Astrocytes (ASTs) play a generally beneficial role in remyelination, including the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) to OLs. However, the specific downstream mechanism is unclear.Methods: This study investigated the proliferation of OPCs in OPCs mono-culture, OPCs culture with ASTs supernatant, and ASTs-OPCs co-culture. Gene Ontology (GO) analysis were used to analyze the differentially expressed genes after transcriptome sequencing of these OPCs. Electron microscope, Nanoparticle Tracking Analysis (NTA), Fluorescence tracing of exosomes and Western blot were used to evaluate the effects of exsomes. Pull-down, co-immunoprecipitation (Co-IP) and mass spectrometry analys were conducted to find the downstream signal proliferation which is transmitted information into OPCs.Reasults: Direct contact co-culture of ASTs and OPCs promotes the proliferation of OPCs. After Cx47 siRNA interference under ASTs-OPCs co-culture, Chi3l1 secretion in exosome reveals associated decrease, and OPCs proliferation decreased. The cell proliferation induced by Chi3l1 was inhibited after siRNA interfered with Myh9, and the expression of cyclin D1 was also decreased.Conclusions: These results suggest that ASTs transmit information to OPCs by increasing gap junction channel Cx47, thereby promoting the secretion of Chi3l1 in exosome of OPCs. The secretory form of Chi3l1 in exosome might be easier to enter the target cell than in extracellular supernatant, which is beneficial to the activation of Myh9 to promote OPCs proliferation. This may be a potential target for drugs rescuing neurodegeneration diseases related to remyelination.

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Faculty Opinions recommendation of Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737829927.793575795 ◽

2020 ◽

Author(s):

Jacqueline Trotter

Keyword(s):

Major Depressive Disorder ◽

Prefrontal Cortex ◽

Depressive Disorder ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Major Depressive ◽

Excitatory Neurons ◽

Single Nucleus ◽

Oligodendrocyte Precursor

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Culture, identification and characterization of rat oligodendrocyte precursor cells in vitro

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2012.00130 ◽

2012 ◽

Vol 32 (2) ◽

pp. 130-135

Author(s):

Mei-lan CHEN ◽

Zhong-jun TANG ◽

Jian MING ◽

Hao WANG ◽

Chun HU ◽

...

Keyword(s):

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Oligodendrocyte Precursor ◽

Culture Identification ◽

Identification And Characterization

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Neuroinflammation in Demyelinating Diseases: Oxidative Stress as a Modulator of Glial Cross-Talk

Current Pharmaceutical Design ◽

10.2174/1381612825666191216125725 ◽

2020 ◽

Vol 25 (45) ◽

pp. 4755-4762 ◽

Cited By ~ 3

Author(s):

Rodrigo Varas ◽

Fernando C. Ortiz

Keyword(s):

Oxidative Stress ◽

Action Potentials ◽

Cell Interaction ◽

Demyelinating Diseases ◽

Signal Molecules ◽

Oligodendrocyte Precursor Cells ◽

Cytokines And Chemokines ◽

Regulatory Aspect ◽

Saltatory Conduction ◽

Oligodendrocyte Precursor

: Myelin is a specialized membrane allowing for saltatory conduction of action potentials in neurons, an essential process to achieve the normal communication across the nervous system. Accordingly, in diseases characterized by the loss of myelin and myelin forming cells -oligodendrocytes in the CNS-, patients show severe neurological disabilities. After a demyelinated insult, microglia, astrocytes and oligodendrocyte precursor cells invade the lesioned area initiating a spontaneous process of myelin repair (i.e. remyelination). A preserved hallmark of this neuroinflammatory scenario is a local increase of oxidative stress, where several cytokines and chemokines are released by glial and other cells. This generates an environment that determines cell interaction resulting in oligodendrocyte maturity and the ability to synthesize new myelin. Herein we review the main features of the regulatory aspect of these molecules based on recent findings and propose new putative signal molecules involved in the remyelination process, focused in the etiology of Multiple Sclerosis, one of the main demyelinating diseases causing disabilities in the population.

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Oxidative Stress, Ocular Disease and Diabetes Retinopathy

Current Pharmaceutical Design ◽

10.2174/1381612825666190115121531 ◽

2019 ◽

Vol 24 (40) ◽

pp. 4726-4741 ◽

Cited By ~ 8

Author(s):

Orathai Tangvarasittichai ◽

Surapon Tangvarasittichai

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Cell Death ◽

Protein Modification ◽

Morphological Changes ◽

Corneal Dystrophy ◽

Age Related Macular Degeneration ◽

Ocular Diseases ◽

Retinal Light Damage ◽

Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

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