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Cited by 22Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

BCAS1-positive immature oligodendrocytes are affected by the α-synuclein-induced pathology of multiple system atrophy

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Kaji, Seiji, Maki, Takakuni, Ueda, Jun, Ishimoto, Tomoyuki, Inoue, Yutaka, Yasuda, Ken, Sawamura, Masanori, Hikawa, Rie +3 more·2020·Acta Neuropathologica Communications
DOI 10.1186/s40478-020-00997-4PMC PMC7391509
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Abstract

Multiple system atrophy (MSA) is pathologically characterized by the presence of fibrillar α-synuclein-immunoreactive inclusions in oligodendrocytes. Although the myelinating process of oligodendrocytes can be observed in adult human brains, little is known regarding the presence of α-synuclein pathology in immature oligodendrocytes and how their maturation and myelination are affected in MSA brains. Recently, breast carcinoma amplified sequence 1 (BCAS1) has been found to be specifically expressed in immature oligodendrocytes undergoing maturation and myelination. Here, we analyzed the altered dynamics of oligodendroglial maturation in both MSA brains and primary oligodendroglial cell cultures which were incubated with α-synuclein pre-formed fibrils. The numbers of BCAS1-expressing oligodendrocytes that displayed a matured morphology negatively correlated with the density of pathological inclusions in MSA brains but not with that in Parkinson’s disease and diffuse Lewy body disease. In addition, a portion of the BCAS1-expressing oligodendrocyte population showed cytoplasmic inclusions, which were labeled with antibodies against phosphorylated α-synuclein and cleaved caspase-9. Further in vitro examination indicated that the α-synuclein pre-formed fibrils induced cytoplasmic inclusions in the majority of BCAS1-expressing oligodendrocytes. In contrast, the majority of BCAS1-non-expressing mature oligodendrocytes did not develop inclusions on day 4 after maturation induction. Furthermore, exposure of α-synuclein pre-formed fibrils in the BCAS1-positive phase caused a reduction in oligodendroglial cell viability. Our results indicated that oligodendroglial maturation and myelination are impaired in the BCAS1-positive phase of MSA brains, which may lead to the insufficient replacement of defective oligodendrocytes. In vitro, the high susceptibility of BCAS1-expressing primary oligodendrocytes to the extracellular α-synuclein pre-formed fibrils suggests the involvement of insufficient oligodendroglial maturation in MSA disease progression and support the hypothesis that the BCAS1-positive oligodendrocyte lineage cells are prone to take up aggregated α-synuclein in vivo.

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  • Actively myelinating oligodendrocytes are responsible for the ongoing formation and repair of myelin during the demyelinating process observed in multiple sclerosis and multiple system atrophy.

    “Actively myelinating oligodendrocytes are responsible for the ongoing formation and repair of myelin during the demyelinating process observed in multiple sclerosis and multiple system atrophy. 29 , 30”

    From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [29]

    The Introduction identifies BCAS1-positive immature oligodendrocytes as present during active myelination and remyelination and reports their increase in remyelinating areas of multiple sclerosis. For multiple system atrophy, however, the Conclusions report impaired oligodendroglial maturation and regeneration, not successful ongoing myelin repair. Page numbers are not available in the supplied copy. (LLM, conf=0.86)

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  • BCAS1+ oligodendrocytes in the cortex appear in two main phenotypes: resting cells with few or no immunopositive processes, prevailing in the healthy adult brain, and activated cells with pre-myelinating/myelinating morphology characterized by internode formation.

    “BCAS1+ oligodendrocytes in the cortex appear in two main phenotypes: cells with few or no immunopositive processes, prevailing in the healthy adult brain (‘resting’ BCAS1+ oligodendrocytes; arrows in Fig. 1A) and cells with a pre-myelinating morphology with multiple branches and myelinating morphology, characterized by internode formation (‘activated’ BCAS1+ oligodendrocytes; arrowheads in Fig. 1A”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [31]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • BCAS1+ oligodendrocytes are Olig2+ but do not express markers of oligodendrocyte precursor cells (e.g. NG2) and mature oligodendrocytes (e.g. CC1 or p25/TTTP), representing an intermediate stage of oligodendrocyte differentiation.

    “BCAS1+ oligodendrocytes are Olig2+ but do not express markers of oligodendrocyte precursor cells (e.g. NG2) and mature oligodendrocytes (e.g. CC1 or p25/TTTP), thus representing an intermediate stage of oligodendrocyte differentiation.”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [31]

    The Introduction identifies BCAS1-positive cells as immature, differentiating oligodendrocytes that express OLIG2 and show limited labeling for precursor and mature-cell markers. The claim overstates this as no expression: the paper reports NG2 labeling in 3.5% of these cells and TPPP/p25α labeling in 0.6%, although CC1 labeling was 0%. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • BCAS1 identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration.

    “Brain-enriched myelin-associated protein 1 (BCAS1) identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration.”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [31]

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Research works printed but not linked: 19

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Authors
Kaji, S., Maki, T., Ueda, J., Ishimoto, T., Inoue, Y., Yasuda, K., Sawamura, M., Hikawa, R., Ayaki, T., Yamakado, H., & Takahashi, R.
Affiliations
Kyoto University (JP)
Corresponding author
Maki, Takakuni
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2020-07-29
Volume
8
Issue
1
Pages
120-120
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-020-00997-4
PMC
PMC7391509
OpenAlex
W3045617313
Cited by
22
References
3
Citations by year
2026: 1 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 2
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Japan Agency for Medical Research and Development (18ek0109384h0001, 19ek0109384h0002)
  • Kyoto University MSA Research Fund
  • Grant-in-Aid for Research Activity start-up from Japan Society for the Promotion of Science (18H06088)
  • Grant-in-Aid for Young Scientists (B) from Japan Society for the Promotion of Science (19K16915)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
multiple system atrophy, BCAS1, oligodendrocyte maturation, myelination, alpha-synuclein fibrils, cytoplasmic inclusions, phosphorylated alpha-synuclein, caspase-9, Parkinson's disease, dementia with Lewy bodies, oligodendroglial lineage
MeSH terms
Oligodendrocyte Precursor Cells, Animals, Cell Differentiation, Humans, Neoplasm Proteins, Nerve Tissue Proteins, Oligodendroglia, Rats, Sprague-Dawley, Multiple System Atrophy, Rats, alpha-Synuclein

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