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Abstract Details

Oligodendrogenesis following cortical demyelination generates a novel myelination pattern
Multiple Sclerosis
S55 - MS Basic Science (4:58 PM-5:09 PM)
009

Cortical demyelination plays a critical role in the pathogenesis of progressive multiple sclerosis (MS), leading to physical and cognitive disability and brain atrophy. It is not known whether the pattern of cortical myelination is re-established following injury.

To monitor the spatial and temporal dynamics of remyelination in the cerebral cortex of mice.  

MOBP-EGFP transgenic mice aged 8-10 weeks old were fed the oligodendrocyte toxin, cuprizone (0.2%), for three weeks and resulting changes in myelination were followed by repeated two-photon imaging through chronic cranial windows implanted over the somatosensory cortex.

Cuprizone exposure induced near complete oligodendrocyte loss and demyelination in the upper layers of the cortex within five weeks. Newly formed oligodendrocytes appeared at a much higher rate than the generation of new oligodendrocytes in control mice. Oligodendrocyte cell bodies appeared in locations distinct from those occupied prior to cuprizone exposure, demonstrating that the global pattern of oligodendrocytes is not maintained after injury. Remyelinating oligodendrocytes formed new internodes that, after an initial period of remodeling, remained remarkably stable. Single remyelinating oligodendrocytes replaced sheaths and formed sheaths around axons that were previously unmyelinated, thereby generating a novel myelination pattern. In cases of internode replacement, nodes of Ranvier often appeared in a similar location, suggesting that key molecular cues that define the placement of myelin are preserved after myelin is lost. Sensory enrichment after demyelination appeared to prevent the loss of some oligodendrocytes, helping to preserve the pattern of myelination formed prior to injury.

The ability to monitor remyelination of individual axons in living animals offers new opportunities for defining the mechanisms of oligodendrogenesis and axon recognition, as well as evaluating the effectiveness of potential therapeutics in vivo.

Authors/Disclosures
Jennifer L. Orthmann Murphy, MD, PhD (Hospital of the University of Pennsylvania)
PRESENTER
Dr. Orthmann Murphy has received personal compensation in the range of $0-$499 for serving as a Consultant for Vigil Neuroscience. Dr. Orthmann Murphy has received personal compensation in the range of $0-$499 for serving as a Consultant for NovoGlia. The institution of Dr. Orthmann Murphy has received research support from Vigil Neurosciences. The institution of Dr. Orthmann Murphy has received research support from National MS Society. The institution of Dr. Orthmann Murphy has received research support from Fishman Family Foundation. The institution of Dr. Orthmann Murphy has received research support from Global Leukodystrophy Initiative Clinical Trial Network. The institution of Dr. Orthmann Murphy has received research support from NINDS. The institution of Dr. Orthmann Murphy has received research support from Montague Investigator Award. Dr. Orthmann Murphy has received personal compensation in the range of $500-$4,999 for serving as a Developing CME content on Neurogenetics with American Neurological Association. Dr. Orthmann Murphy has received personal compensation in the range of $500-$4,999 for serving as a Faculty, Honoraria with CMSC.
No disclosure on file
No disclosure on file
Peter A. Calabresi, MD, FAAN (Johns Hopkins University) Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.
No disclosure on file