Longitudinal Intravital Microscopy Reveals Axon Degeneration Concomitant With Inflammatory Cell Infiltration in an LPC Model of Demyelination

Bilal El Waly (1, 2) , Emeline Buttigieg (3, 1, 2) , Cem Karakus (1, 2) , Sophie Brustlein (4, 2) , Franck Debarbieux (1, 2)

1 INT - Institut de Neurosciences de la Timone
2 CERIMED - Centre Européen de Recherche en Imagerie médicale
3 Department of Physiology, and Center for Integrative Physiology and Molecular Medicine
4 IBDM - Institut de Biologie du Développement de Marseille

Demyelination and axon degeneration are major events in all neurodegenerative diseases, including multiple sclerosis. Intoxication of oligodendrocytes with lysophosphatidylcholine (LPC) is often used as a selective model of focal and reversible demyelination thought to have no incidence for neurons. To characterize the cascade of cellular events involved in LPC-induced demyelination, we have combined intravital coherent antistoke Raman scattering microscopy with intravital two-photon fluorescence microscopy in multicolor transgenic reporter mice. Moreover, taking advantage of a unique technique of spinal glass window implantation, we here provide the first longitudinal description of cell dynamics in the same volume of interest over weeks after insults. We have detected several patterns of axon–myelin interactions and classified them in early and advanced events. Unexpectedly, we have found that oligodendrocyte damages are followed by axon degeneration within 2 days after LPC incubation, and this degeneration is amplified after the recruitment of the peripheral proinflammatory cells at day 4. Beyond day 7, the recovery of axon number and myelin takes 3 more weeks postlesion and involves a new wave of anti-inflammatory innate immune cells at day 14. Therefore, recurrent imaging over several weeks suggests an important role of peripheral immune cells in regulating both the axonal and oligodendroglial fates and thereby the remyelination status. Better understanding the recruitment of peripheral immune cells during demyelinating events should help to improve diagnosis and therapy.

Mots clés: lysophosphatidylcholine; demyelination; neurodegeneration innate immune cells; CARS; spinal glass window

Domaines: Sciences du Vivant [q-bio]

Bilal El Waly, Emeline Buttigieg, Cem Karakus, Sophie Brustlein, Franck Debarbieux. Longitudinal Intravital Microscopy Reveals Axon Degeneration Concomitant With Inflammatory Cell Infiltration in an LPC Model of Demyelination. Frontiers in Cellular Neuroscience, 2020, 14, ⟨10.3389/fncel.2020.00165⟩. ⟨hal-03141499⟩