Maintenance of the relative proportion of oligodendrocytes to axons even in the absence of BAX and BAK
Open accessAbstract
Highly purified oligodendroglial lineage cells from mice lacking functional bax and bak genes were resistant to apoptosis after in-vitro differentiation, indicating an essential role of the intrinsic apoptotic pathway in apoptosis of oligodendrocytes in the absence of neurons (axons) and other glial cells. These mice therefore provide a valuable tool with which to evaluate the significance of the intrinsic apoptotic pathway in regulating the population sizes of oligodendrocytes and oligodendroglial progenitor cells. Quantitative analysis of the optic nerves and the dorsal columns of the spinal cord revealed that the absolute numbers of mature oligodendrocytes immunolabeled for aspartoacylase and adult glial progenitor cells expressing NG2 chondroitin sulfate proteoglycan were increased in both white matter tracts of adult bax/bak-deficient mice and, to a lesser extent, bax-deficient mice, except that there was no increase in NG2-positive progenitor cells in the dorsal columns of these strains of mutant mice. These increases in mature oligodendrocytes and progenitor cells in bax/bak-deficient mice were unexpectedly proportional to increases in numbers of axons in these white matter tracts, thus retaining the oligodendroglial lineage to axon ratios of at most 1.3-fold of the physiological numbers. This is in contrast to the prominent expansion in numbers of neural precursor cells in the subventricular zones of these adult mutant mice. Our study indicates that homeostatic control of cell number is different for progenitors of the oligodendroglial and neuronal lineages. Furthermore, regulatory mechanism(s) operating in addition to apoptotic elimination through the intrinsic pathway, appear to prevent the overproduction of highly mitotic oligodendroglial progenitor cells.
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ASPA is a marker of mature oligodendrocytes, and ASPA+ cells overlap 100% with GSTπ and 93% with CC1.
“ASPA is a marker of mature oligodendrocytes. In this population, ASPA positive cells have been reported to overlap 100 and 93% with the widely used oligodendrocyte soma markers glutathione S-transferase π isoform and CC1, respectively (Kawai et al., 2009).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Kawai et al., 2009
The Results section reports that ASPA marks mature oligodendrocytes and that ASPA-positive cells overlapped with almost 100% of GSTπ-positive cells and 93 ± 4% of CC1-positive cells in three adult mice. The citing sentence makes the first figure an exact 100% and omits the uncertainty around the second. (LLM, conf=0.85)
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Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration
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“In this population, ASPA positive cells have been reported to overlap 100 and 93% with the widely used oligodendrocyte soma markers glutathione S-transferase π isoform and CC1, respectively (Kawai et al., 2009).”
BackgroundTamoxifen promotes differentiation of oligodendrocyte progenitors in vitro
Barratt, H. E., Budnick, H. C., Parra, R., Lolley, R. J., Perry, C. N., & Nesic, O. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.01.026 · Cited by 22 · see citing works
- Authors
- Kawai, K., Itoh, T., Itoh, A., Horiuchi, M., Wakayama, K., Bannerman, P., Garbern, J. Y., Pleasure, D., & Lindsten, T.
- Affiliations
- Shriners Hospitals for Children - Northern California (US)
- Wayne State University (US)
- University of Pennsylvania (US)
- Corresponding author
- Itoh, Aki
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2009-11-30
- Volume
- 30
- Issue
- 11
- Pages
- 2030-2041
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC2830116
- OpenAlex
- W2069025840
- Cited by
- 21
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2018: 2 · 2016: 3 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS025044, R01NS025044)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- oligodendrocytes, axons, Bax, Bak, mitochondrial apoptosis, apoptosis, aspartoacylase, white matter, optic nerve, spinal cord dorsal columns, glial lineage
- MeSH terms
- Chondroitin Sulfate Proteoglycan 4, Animals, Animals, Newborn, Antigens, Axons, Brain, Cell Differentiation, Cells, Cultured, Myelin Basic Protein, Gangliosides, Gene Expression Regulation, Myelin Sheath, Oligodendroglia, Optic Nerve, Proteoglycans, RNA, Messenger, Stem Cells, Time Factors, Cell Death, Apoptosis, Mice, Knockout, O Antigens, In Situ Nick-End Labeling, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice, Proto-Oncogene Proteins c-bcl-6
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