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Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia
Open accessAbstract
Introduction: Nerve growth factor (NGF) is a pleiotropic molecule acting on different cell types in physiological and pathological conditions. However, the effect of NGF on the survival, differentiation and maturation of oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), the cells responsible for myelin formation, turnover, and repair in the central nervous system (CNS), is still poorly understood and heavily debated. Methods: Here we used mixed neural stem cell (NSC)-derived OPC/astrocyte cultures to clarify the role of NGF throughout the entire process of OL differentiation and investigate its putative role in OPC protection under pathological conditions. Results: We first showed that the gene expression of all the neurotrophin receptors (TrkA, TrkB, TrkC, and p75 NTR) dynamically changes during the differentiation. However, only TrkA and p75 NTR expression depends on T3-differentiation induction, as Ngf gene expression induction and protein secretion in the culture medium. Moreover, in the mixed culture, astrocytes are the main producer of NGF protein, and OPCs express both TrkA and p75 NTR. NGF treatment increases the percentage of mature OLs, while NGF blocking by neutralizing antibody and TRKA antagonist impairs OPC differentiation. Moreover, both NGF exposure and astrocyte-conditioned medium protect OPCs exposed to oxygenglucose deprivation (OGD) from cell death and NGF induces an increase of AKT/pAKT levels in OPCs nuclei by TRKA activation. Discussion: This study demonstrated that NGF is implicated in OPC differentiation, maturation, and protection in the presence of metabolic challenges, also suggesting implications for the treatment of demyelinating lesions and diseases.
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Potential disruption in communication with vulnerable Sst supertypes may impact myelination.
“The cognate receptor for NGF and NGFR is expressed specifically in oligodendrocytes and OPCs, suggesting potential disruption in communication with vulnerable Sst supertypes that may impact myelination59.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [59]
The Results (§3.1, page unavailable) report NGF receptors in OPCs, and the Introduction links communication with OPCs to myelination. The paper does not address vulnerable Sst supertypes or suggest that disrupted communication with them affects myelination; it also does not establish that receptor expression is specific to oligodendrocytes and OPCs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe cognate receptor for NGF and NGFR is expressed specifically in oligodendrocytes and OPCs.
“The cognate receptor for NGF and NGFR is expressed specifically in oligodendrocytes and OPCs, suggesting potential disruption in communication with vulnerable Sst supertypes that may impact myelination59.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [59]
Results §3.1 and the Discussion report that PDGFαR-positive OPCs express the NGF receptors TRKA and p75NTR, and examine receptor expression during OPC differentiation and oligodendrocyte maturation. They do not establish that these receptors are expressed specifically in oligodendrocytes and OPCs; the Discussion also describes neurons as a major NGF target. The sentence’s proposed communication with Sst supertypes is the citing authors’ inference, not a finding attributed to this source. (LLM, conf=0.84)
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Kessaris, N., Fogarty, M., Iannarelli, P., Grist, M., Wegner, M., & Richardson, W. D. (2006) · Nature Neuroscience · doi:10.1038/nn1620 · Cited by 1,195
Extensive piano practicing has regionally specific effects on white matter development
Bengtsson, S. L., Nagy, Z., Skare, S., Forsman, L., Forssberg, H., & Ullén, F. (2005) · Nature Neuroscience · doi:10.1038/nn1516 · Cited by 1,193
Dynamics of Oligodendrocyte Generation and Myelination in the Human Brain
Yeung, M. S. Y., Zdunek, S., Bergmann, O., Bernard, S., Salehpour, M., Alkass, K., Perl, S., Tisdale, J., Possnert, G., Brundin, L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.011 · Cited by 541
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Integrated multimodal cell atlas of Alzheimer’s disease
Gabitto, M. I., Travaglini, K. J., Rachleff, V. M., Kaplan, E. S., Long, B., Ariza, J., Ding, Y., Mahoney, J. T., Dee, N., Goldy, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01774-5 · Cited by 397
“The cognate receptor for NGF and NGFR is expressed specifically in oligodendrocytes and OPCs, suggesting potential disruption in communication with vulnerable Sst supertypes that may impact myelination 59 .”
Metadata
- Authors
- Baldassarro, V. A., Cescatti, M., Rocco, M. L., Aloe, L., Lorenzini, L., Giardino, L., & Calzà, L.
- Affiliations
- University of Bologna (IT)
- Fondazione IRET ONLUS (IT)
- Corresponding author
- Calzà, Laura
- ORCID
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2023-02-16
- Volume
- 17
- Pages
- 1111170-1111170
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC9978228
- OpenAlex
- W4321107445
- Cited by
- 26
- References
- 3
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 9 · 2023: 1
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques (Role of RXRγ in T3-mediated oligodendrocyte differentiation and remyelination)
- Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR National Technology Clusters project IRMI (CTN01_00177_888744))
- Regione Emilia-Romagna (Mat2Rep, POR-FESR 2014-2020)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- nerve growth factor, oligodendrocyte precursor cells, oligodendrocyte differentiation, hypoxia-ischemia, neurotrophin receptors, TrkA, p75 neurotrophin receptor, astrocytes, neuroprotection, Akt signaling, demyelinating disease, myelination
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