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OFF-TARGET COMPLEMENT-MEDIATED OLIGODENDROCYTE INJURY IN A MOUSE MODEL OF NMOSD
Selin Kenetand 7 co-authors
Technical University of Munich
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-020
Presentation
Date TBA
Board: PS03-08AM-020
Event Information
Poster Board
PS03-08AM-020
Poster
View posterAbstract
The pathological features of neuromyelitis optica spectrum disorder (NMOSD) include astrocyte loss followed by demyelination, yet the mechanisms linking astrocyte injury to secondary oligodendrocyte pathology remain poorly understood. To investigate this, we performed in vivo spinal cord imaging in an acute mouse model of NMOSD, allowing observation of glial injury dynamics at single-cell resolution. Targeted astrocyte depletion induced by AQP4 antibodies led to robust oligodendrocyte injury, marked by early intracellular calcium dysregulation that preceded oligodendrocyte death. Notably, oligodendrocyte injury occurred after a temporal delay relative to astrocyte lysis and without overt membrane damage, indicating a distinct injury mechanism within this glial pair. Oligodendrocyte pathology was driven by soluble complement components released during antibody-mediated astrocyte targeting and was selective among glial cells; microglia and oligodendrocyte precursor cells were spared in NMOSD lesions. Oligodendrocyte-specific expression of the membrane attack complex (MAC) inhibitor CD59 preserved oligodendrocytes despite astrocyte loss, confirming that this is not solely due lack of astrocytic support. Together, these findings reveal a complement-mediated, cell-type-specific vulnerability within the astrocyte-oligodendrocyte glial pair as a key mechanism driving demyelination in NMOSD and suggesting a convergent pathway relevant to other demyelinating diseases.
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