Biology subjects

Eichenseer, K.

Publications and source records attributed to Eichenseer, K..

3 recordsLinked to original sources

bioRxiv2026

Early demyelination by off-target complement injury in a mouse model of neuromyelitis optica

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune CNS disease characterized by serum antibodies targeting astrocytes for complement-mediated lysis. NMOSD lesions show not only astrocyte loss but also early demyelination and oligodendrocyte injury - histological hallmarks that converge with those of other primary demyelinating conditions. How pathology spreads to cause demyelination, particularly in early lesions, remains unclear. Using spinal cord imaging in an acute mouse NMOSD model, we directly observe the spread of pathology from astrocytes to oligodendrocytes in evolving lesions. This spread is characterized by initial calcium dyshomeostasis in oligodendrocytes followed by delayed, non-lytic cell death. Oligodendrocyte death is driven not by astrocyte loss per se but by spill-over of soluble complement proteins, as oligodendrocytes can be cell-autonomously preserved by the cell-type-specific expression of the complement inhibitor CD59. Our findings explain the convergence of glial pathology in antibody-mediated CNS autoimmunity and point towards new approaches to prevent secondary glial injury.

neuroscience↗

bioRxiv2026

Selective Cortical Myelination Reflects Axon-Driven Progression of the BCAS1-positive Oligodendrocyte Lineage

Myelination in the cerebral cortex is sparse, discontinuous, showing marked heterogeneity across cortical areas and along individual axons, yet the mechanisms that establish this complex and selective architecture remain unclear. Using histological mapping of oligodendrocyte lineage cells across cortical areas combined with longitudinal in vivo imaging, we find that initial myelination is highly targeted: up to 80 percent of the earliest segments arise consecutively along the same subset of axons. We observed that oligodendrocyte precursor cells enter a premyelinating BCAS1-positive state even within cortical regions that remain poorly myelinated or unmyelinated. However, the progression beyond early premyelinating morphologies correlates with local myelin levels and with interactions with specific neuronal partners. BCAS1-positive ensheathments show a preferential stabilisation and elongation along parvalbumin interneurons compared with somatostatin interneurons, linking regional neuronal composition to differential myelin levels. These findings indicate that cortical myelination emerges from intrinsic lineage programs that are refined through selective interactions with axons, thereby linking neuronal diversity to cortical myelin distribution and providing a framework to understand why remyelination may fail in regions where myelination supportive neuronal populations are reduced.

neuroscience↗

bioRxiv2026

Local demyelination rekindles oligodendrocyte precursor dynamics and remyelination in old age

Cortical myelination is critical for circuit function, plasticity, and long-term stability in the adult brain. With age and disease, the capacity to restore myelin after oligodendrocyte (OL) loss declines, and this failure is thought to reflect intrinsic limitations of OL precursor cells (OPCs) and a loss of permissive cues within the cortical environment. Here, using single-OL ablations and intravital imaging in mice, we show that as cortical remyelination efficiency declines, OPC motility declines, a phenomenon that can be mimicked by blocking CXCL12/CXCR4 signaling. Counter to prevailing notions, however, we find that even in aging, OPCs retain the capacity to generate new OLs and sheath axons, which can be rekindled by a graded demyelinating stimulus, inducing a more juvenile OPC motile state. This reveals an unrecognized remyelination potential in aging and identifies OPC dynamics as a key determinant of cortical remyelination, a property that could be targeted to improve myelin repair.

neuroscience↗