Oligodendrocytes, the Forgotten Target of Gene Therapy DOI Creative Commons
Yasemin Güneş, Catherine Le Stunff, Pierre Bougnères

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1973 - 1973

Published: Nov. 28, 2024

If the billions of oligodendrocytes (OLs) populating central nervous system (CNS) patients could express their feelings, they would undoubtedly tell gene therapists about frustration with other neural cell populations, neurons, microglia, or astrocytes, which have been favorite targets transfer experiments. This review questions why OLs left out most therapy attempts. The first explanation is that pathogenic role still discussed in CNS diseases. Another reason so-called ubiquitous CAG, CBA, CBh, CMV promoters—widely used studies—are unable poorly able to activate transcription episomal transgene copies brought by adeno-associated virus (AAV) vectors OLs. Accordingly, expression has either not found evaluated studies rodents non-human primates. aims current are give rightful place among cells future target and encourage researchers test effect OL transduction various

Language: Английский

Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes DOI Creative Commons
Jenea M. Bin, Katie Emberley, Tobias J. Buscham

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

SUMMARY Myelination facilitates the rapid conduction of action potentials along axons. In central nervous system (CNS), myelinated axons vary over 100-fold in diameter, with speed scaling linearly increasing diameter. Axon diameter and myelination are closely interlinked, axon exerting a strong influence on myelination. Conversely, myelinating Schwann cells peripheral can both positively negatively affect However, whether is regulated by CNS oligodendrocytes less clear. Here, we investigated growth absence myelin using mouse ( Mbp shi/shi M yrf conditional knockout) zebrafish olig2 morpholino) models. We find that neither ensheathment axons, nor formation compact required for to achieve appropriate diverse diameters. This indicates developmental independent myelination, shows PNS differentially axonal morphology.

Language: Английский

Citations

1
Oligodendrocytes and myelin in aging and disease DOI Creative Commons
Ana Fernández–Sainz, Rocío Rojas, Asier Ruiz

et al.

Ageing & Longevity, Journal Year: 2025, Volume and Issue: 1.2025, P. 46 - 53

Published: Feb. 11, 2025

Oligodendrocytes, the myelinating cells of central nervous system, insulate axons with myelin, enabling rapid signal transmission, supporting neuronal metabolism, and contributing to brain plasticity. However, aging neurodegenerative diseases can significantly impair oligodendrocyte function myelin integrity. During aging, progenitor (OPCs) exhibit a reduced regenerative capacity, leading progressive deterioration cognitive decline. In Alzheimer’s disease, these age-related deficits are exacerbated by neuroinflammation, oxidative stress, amyloid-beta (Aβ) tau pathology, which collectively survival remyelination capacity. Similarly, in Parkinson’s α-synuclein aggregation contributes decline through both shared disease-specific mechanisms. Here, we highlight key features aged diseased oligodendrocytes emphasizing their roles energy plasticity, resilience. Understanding aspects is essential for developing strategies counteract promote neuroprotection diseases.

Language: Английский

Citations

1
Regulators of Oligodendrocyte Differentiation DOI
Ben Emery, Teresa L. Wood

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(6), P. a041358 - a041358

Published: March 19, 2024

Ben Emery1 and Teresa L. Wood2 1Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health & Science University, Portland, 97239, USA 2Department Pharmacology, Physiology Neuroscience, New Jersey Medical School, Rutgers Newark, 07103, Correspondence: terri.wood{at}rutgers.edu

Language: Английский

Citations

6
The gut microbiota–oligodendrocyte axis: A promising pathway for modulating oligodendrocyte homeostasis and demyelination-associated disorders DOI Creative Commons
Wen Tang, Qi Wang,

Mingguang Sun

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 354, P. 122952 - 122952

Published: Aug. 9, 2024

The bidirectional regulation between the gut microbiota and brain, known as gut-brain axis, has received significant attention. myelin sheath, produced by oligodendrocytes or Schwann cells, is essential for efficient nervous signal transmission maintenance of brain function. Growing evidence shows that both oligodendrogenesis myelination are modulated its metabolites, when dysbiosis occurs, changes in composition and/or associated metabolites may impact developmental occurrence neurodevelopmental disabilities. Although link demyelinating disease such multiple sclerosis been extensively studied, our knowledge about role other myelin-related disorders, neurodegenerative diseases, limited. Mechanistically, microbiota-oligodendrocyte axis primarily mediated factors inflammation, vagus nerve, endocrine hormones, evidenced metagenomics, metabolomics, vagotomy, morphological molecular approaches. Treatments targeting this include probiotics, prebiotics, microbial herbal bioactive compounds, specific dietary management. In addition to commonly used approaches, viral vector-mediated tracing gene manipulation, integrated multiomics multicenter clinical trials will greatly promote mechanistic interventional studies ultimately, development new preventive therapeutic strategies against gut-oligodendrocyte axis-mediated impairments. Interestingly, recent findings showed can be induced hippocampal damage reversible myelin-targeted drugs, which provides insights into understanding how hippocampus-based functional impairment (such Alzheimer's disease) regulates peripheral homeostasis systemic disorders.

Language: Английский

Citations

4
White matter aging and its impact on brain function DOI Creative Commons
Janos Groh, Mikael Simons

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase matter hyperintensities. These changes are closely linked to cognitive decline neurological disabilities. The deterioration myelin its diminished ability regenerate as we age further contribute the progression neurodegenerative disorders. Understanding these is crucial for devising effective disease prevention strategies. Here, will discuss alterations that occur with aging examine cellular molecular mechanisms driving aging-related transformations. We highlight how progressive disruption may initiate self-perpetuating cycle inflammation neural damage.

Language: Английский

Citations

4
The Pericellular Function of Fibulin-7 in the Adhesion of Oligodendrocyte Lineage Cells to Neuronal Axons during CNS Myelination DOI

Momona Yamada,

Binri Sasaki,

Nanako Yamada

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 748, P. 151271 - 151271

Published: Jan. 2, 2025

Language: Английский

Citations

0
Gut microbiota regulates optic nerve fiber myelination DOI Creative Commons
Giulia Ronchi, Daniela Pellegrino, Marwa El Soury

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 20, 2025

Recent evidence supports the hypothesis of an association between gut microbiota and pathogenesis retinal eye diseases, suggesting existence a gut-eye axis. However, no data are available on possible effect optic nerve fiber maturation myelin development. We investigated impact nerves collected from neonatal young adult germ-free (GF), gnotobiotic (stably colonized with 12 bacteria strains, OMM12) control (colonized complex microbiota, CGM) mice, by performing stereological morphoquantitative analyses transmission electron microscopy gene expression analysis quantitative real-time PCR. Young GF OMM12 axons smaller hypermyelinated compared to CGM ones, while such differences were detected in nerves. The transcription factors Olig1, Olig2, Sox10 (oligodendrocyte myelination positive regulators) downregulated mice respective neonates. Such developmental downregulation was not observed nerves, that absence prolongs stimulation myelination, possibly through mechanisms yet be identified. Altogether, these underscore pivotal role driving contributing our knowledge about both axis gut-brain axis, opening new horizons for further investigations will explore also pathologies, injuries regeneration associated nerve.

Language: Английский

Citations

0
Electroacupuncture promotes oligodendrocyte differentiation and myelin repair in a rat model of vascular dementia: Investigation of the mechanism from NF-κB-mediated inflammation DOI
Chang Liu, Huayi Yin, Xiaoyu Chen

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Three-Dimensional Design and Implementation of a Dual Compartment Imaging Chamber to Assess Effects of Hypertonic Saline on Periaxonal Swelling and Axonal Spheroid Formation Following Cervical Contusive Spinal Cord Injury in Real Time DOI

Francisco Cortez-Thomas,

Spencer Ames,

Sarayu Alli

et al.

Journal of Neurotrauma, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Contusive and compressive spinal cord injury (SCI) induces pathological changes to white matter (WM) including periaxonal swelling resultant disruption of the axomyelinic interface, axonal swelling/spheroid formation, secondary transection. To further our knowledge role vascular edema in these WM, we designed, three-dimensional (3D) printed a dual-compartment imaging chamber separated by semipermeable membrane mimic manipulate interstitial fluid compartments real time. We hypothesized that hypertonic saline (HTS) applied "vascular" would osmotically shift out space preserve myelinated fibers after SCI. Adult male female 6- 8-week-old Thy1YFP+ transgenic mice underwent C5, mild contusive SCI (30 kilodyne, IH Impactor) vivo, their cords were harvested for ex vivo imaging. Utilizing longitudinal two-photon excitation microscopy (2PE), imaged both myelin (Nile red) axons (YFP+) simultaneously up 4 h C5 conditions induced significant increases spheroid formation within dorsal column over In contrast, perfusion 3% 5% HTS compartment beginning 30 min was highly protective significantly reduced from 1 last hour recorded (4 post-SCI) compared normal (NS) controls. At 2 post-SCI, treatment with (Kruskal-Wallis ANOVA on Ranks, H(3) = 3, p 0.05, n 5-6/group) NS (median, 25th percentile; 11.00, 4.00 versus 9.00, 7.00 48.00, 29.50, respectively; Dunn's method, < 0.05). By (H(3) 15.74, 0.001, decreased spheroids (5.00, 3.00 4.00, 95.00, 38.75, respectively). 7.5% had no beneficial effect. Collectively, data provide insight into dynamic interplay between exchange following Delayed administration increased survival swellings 24 post control, validating translatability dual (mean, standard deviation; 58.09, 3.34 32.08, 5.98, 0.003; 595.19, 326.10 1525.25, 259.82, 0.018, Our findings suggest low-dose solutions may have effect part mitigating thereby potentially reducing occurrence denuded regions. These results enhance understanding degeneration mechanisms hold promise targeted therapeutic interventions improve outcomes

Language: Английский

Citations

0
The Exciting Frontier of Neuroplasticity: Innovations in Brain Health and Recovery DOI Open Access
Ramendra N. Saha

Journal of Behavioral and Brain Science, Journal Year: 2025, Volume and Issue: 15(03), P. 47 - 80

Published: Jan. 1, 2025

Language: Английский

Citations

0