Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis
IntroductionRemyelination of demyelinated axons can occur as an endogenous repair mechanism in multiple sclerosis (MS), but its efficacy varies between both MS individuals and lesions. The molecular and cellular mechanisms that drive remyelination remain poorly understood. Here, we studied the relat...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1522381/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841540169713319936 |
|---|---|
| author | J. Q. Alida Chen Dennis D. Wever Niamh B. McNamara Morjana Bourik Joost Smolders Jörg Hamann Jörg Hamann Inge Huitinga Inge Huitinga |
| author_facet | J. Q. Alida Chen Dennis D. Wever Niamh B. McNamara Morjana Bourik Joost Smolders Jörg Hamann Jörg Hamann Inge Huitinga Inge Huitinga |
| author_sort | J. Q. Alida Chen |
| collection | DOAJ |
| description | IntroductionRemyelination of demyelinated axons can occur as an endogenous repair mechanism in multiple sclerosis (MS), but its efficacy varies between both MS individuals and lesions. The molecular and cellular mechanisms that drive remyelination remain poorly understood. Here, we studied the relation between microglia activation and remyelination activity in MS.MethodsWe correlated regenerative (CD163+) and inflammatory (iNOS+) microglia with BCAS1+ oligodendrocytes, subdivided into early-stage (<3 processes) and late-stage (≥3 processes) cells in brain donors with high or low remyelinating potential in remyelinated lesions and active lesions with ramified/amoeboid (non-foamy) or foamy microglia. A cohort of MS donors categorized as efficiently remyelinating donors (ERDs; n=25) or poorly remyelinating donors (PRDs; n=17) was included, based on their proportion of remyelinated lesions at autopsy.Results and discussionWe hypothesized more CD163+ microglia and BCAS1+ oligodendrocytes in remyelinated and active non-foamy lesions from ERDs and more iNOS+ microglia with fewer BCAS1+ oligodendrocytes in active foamy lesions from PRDs. For CD163+ microglia, however, no differences were observed between MS lesions and MS donor groups. In line with our hypothesis, we found that INOS+ microglia were significantly increased in PRDs compared to ERDs within remyelinated lesions. MS lesions, more late-stage BCAS1+ oligodendrocytes were detected in active lesions with non-foamy or foamy microglia in comparison with remyelinated lesions. Although no differences were found for early-stage BCAS1+ oligodendrocytes between MS lesions, we did find significantly more early-stage BCAS1+ oligodendrocytes in PRDs vs ERDs in remyelinated lesions. Interestingly, a positive correlation was identified between iNOS+ microglia and the presence of early-stage BCAS1+ oligodendrocytes. These findings suggest that impaired maturation of early-stage BCAS1+ oligodendrocytes, encountering inflammatory microglia, may underlie remyelination deficits and unsuccessful lesion repair in MS. |
| format | Article |
| id | doaj-art-07efa34de4074da3adbd08ca1cd6bb71 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-07efa34de4074da3adbd08ca1cd6bb712025-01-14T05:10:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15223811522381Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosisJ. Q. Alida Chen0Dennis D. Wever1Niamh B. McNamara2Morjana Bourik3Joost Smolders4Jörg Hamann5Jörg Hamann6Inge Huitinga7Inge Huitinga8Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, NetherlandsDepartments of Neurology and Immunology, MS Center ErasMS, Erasmus MC, University Medical Center, Rotterdam, NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, NetherlandsDepartment of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Amsterdam, NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, NetherlandsSwammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, NetherlandsIntroductionRemyelination of demyelinated axons can occur as an endogenous repair mechanism in multiple sclerosis (MS), but its efficacy varies between both MS individuals and lesions. The molecular and cellular mechanisms that drive remyelination remain poorly understood. Here, we studied the relation between microglia activation and remyelination activity in MS.MethodsWe correlated regenerative (CD163+) and inflammatory (iNOS+) microglia with BCAS1+ oligodendrocytes, subdivided into early-stage (<3 processes) and late-stage (≥3 processes) cells in brain donors with high or low remyelinating potential in remyelinated lesions and active lesions with ramified/amoeboid (non-foamy) or foamy microglia. A cohort of MS donors categorized as efficiently remyelinating donors (ERDs; n=25) or poorly remyelinating donors (PRDs; n=17) was included, based on their proportion of remyelinated lesions at autopsy.Results and discussionWe hypothesized more CD163+ microglia and BCAS1+ oligodendrocytes in remyelinated and active non-foamy lesions from ERDs and more iNOS+ microglia with fewer BCAS1+ oligodendrocytes in active foamy lesions from PRDs. For CD163+ microglia, however, no differences were observed between MS lesions and MS donor groups. In line with our hypothesis, we found that INOS+ microglia were significantly increased in PRDs compared to ERDs within remyelinated lesions. MS lesions, more late-stage BCAS1+ oligodendrocytes were detected in active lesions with non-foamy or foamy microglia in comparison with remyelinated lesions. Although no differences were found for early-stage BCAS1+ oligodendrocytes between MS lesions, we did find significantly more early-stage BCAS1+ oligodendrocytes in PRDs vs ERDs in remyelinated lesions. Interestingly, a positive correlation was identified between iNOS+ microglia and the presence of early-stage BCAS1+ oligodendrocytes. These findings suggest that impaired maturation of early-stage BCAS1+ oligodendrocytes, encountering inflammatory microglia, may underlie remyelination deficits and unsuccessful lesion repair in MS.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1522381/fullmultiple sclerosisremyelinationinflammationmicrogliaoligodendrocytes |
| spellingShingle | J. Q. Alida Chen Dennis D. Wever Niamh B. McNamara Morjana Bourik Joost Smolders Jörg Hamann Jörg Hamann Inge Huitinga Inge Huitinga Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis Frontiers in Immunology multiple sclerosis remyelination inflammation microglia oligodendrocytes |
| title | Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis |
| title_full | Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis |
| title_fullStr | Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis |
| title_full_unstemmed | Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis |
| title_short | Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis |
| title_sort | inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis |
| topic | multiple sclerosis remyelination inflammation microglia oligodendrocytes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1522381/full |
| work_keys_str_mv | AT jqalidachen inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT dennisdwever inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT niamhbmcnamara inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT morjanabourik inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT joostsmolders inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT jorghamann inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT jorghamann inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT ingehuitinga inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis AT ingehuitinga inflammatorymicrogliacorrelatewithimpairedoligodendrocytematurationinmultiplesclerosis |