Contributions
Abstract: 218
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Myelination of axons is an essential step to ensure the rapid propagation of action potentials by saltatory conduction, which relies on the nodes of Ranvier, short unmyelinated domains highly enriched in voltage-gated sodium channels (Nav). In demyelinating diseases such as multiple sclerosis (MS), nodes of Ranvier are disrupted resulting in conduction alteration. Nav can be detected at discrete domains before remyelination in partially remyelinated MS lesions, suggesting that this early reassembly might influence the repair process. Furthermore, in recent ex vivo and in vivo studies in mice, contacts between microglia and nodes of Ranvier have been observed in myelinated tissue and in a (re)myelinating context. These contacts have been shown stable and increasing in a remyelinating context, suggesting a potential role on the repair processes.
Aims: To corroborate the existence of microglia-nodes of Ranvier interactions in post-mortem control and MS human brain tissues, to quantify this interaction in different lesion types and to characterize the phenotype of the “contacting” microglia.
Methods: We performed a neuropathology study on post-mortem from 3 controls and 10 MS brains, focusing on various types of lesions: normal appearing white matter (NAWM), pre-active lesions, active lesions with ongoing demyelination and shadow plaques (fully remyelinated). By using immunohistochemistry, we analysed the distribution of nodal proteins (Nav, Nav1.6) and the potential interactions with specific microglial markers, such as MHC-II (activated microglia/macrophages), TMEM119 (resident microglia), CD68 (pro-inflammatory), CCL22 (pro-remyelinating).
Results: Contacts between microglia and nodes of Ranvier have been detected in control tissues, within pre-active lesions, at the border of active demyelinated MS lesions and in shadow plaques. The number of “contacted” Nodes of Ranvier higher in MS tissues than in controls. Interestingly, most of the cells contacting the nodes are TMEM119 positive, indicating that they correspond to resident microglia cells, rather than recruited blood-derived macrophages.
Conclusions: These data, uncovering the existence of interactions between nodal axonal domains and microglial cells, suggest an early key role of innate immunity in axonal pathological alterations both in active demyelination and in remyelinating processes. This may open new perspective studies on intercellular mechanisms regulating MS remyelination.
Disclosure: T. Roux: nothing to disclose
R. Magliozzi: nothing to disclose
M. S. Aigrot: nothing to disclose
Valentina Mazziotti: nothing to disclose
C. Lubetzki: nothing to disclose
A. Desmazières: nothing to disclose
Abstract: 218
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Myelination of axons is an essential step to ensure the rapid propagation of action potentials by saltatory conduction, which relies on the nodes of Ranvier, short unmyelinated domains highly enriched in voltage-gated sodium channels (Nav). In demyelinating diseases such as multiple sclerosis (MS), nodes of Ranvier are disrupted resulting in conduction alteration. Nav can be detected at discrete domains before remyelination in partially remyelinated MS lesions, suggesting that this early reassembly might influence the repair process. Furthermore, in recent ex vivo and in vivo studies in mice, contacts between microglia and nodes of Ranvier have been observed in myelinated tissue and in a (re)myelinating context. These contacts have been shown stable and increasing in a remyelinating context, suggesting a potential role on the repair processes.
Aims: To corroborate the existence of microglia-nodes of Ranvier interactions in post-mortem control and MS human brain tissues, to quantify this interaction in different lesion types and to characterize the phenotype of the “contacting” microglia.
Methods: We performed a neuropathology study on post-mortem from 3 controls and 10 MS brains, focusing on various types of lesions: normal appearing white matter (NAWM), pre-active lesions, active lesions with ongoing demyelination and shadow plaques (fully remyelinated). By using immunohistochemistry, we analysed the distribution of nodal proteins (Nav, Nav1.6) and the potential interactions with specific microglial markers, such as MHC-II (activated microglia/macrophages), TMEM119 (resident microglia), CD68 (pro-inflammatory), CCL22 (pro-remyelinating).
Results: Contacts between microglia and nodes of Ranvier have been detected in control tissues, within pre-active lesions, at the border of active demyelinated MS lesions and in shadow plaques. The number of “contacted” Nodes of Ranvier higher in MS tissues than in controls. Interestingly, most of the cells contacting the nodes are TMEM119 positive, indicating that they correspond to resident microglia cells, rather than recruited blood-derived macrophages.
Conclusions: These data, uncovering the existence of interactions between nodal axonal domains and microglial cells, suggest an early key role of innate immunity in axonal pathological alterations both in active demyelination and in remyelinating processes. This may open new perspective studies on intercellular mechanisms regulating MS remyelination.
Disclosure: T. Roux: nothing to disclose
R. Magliozzi: nothing to disclose
M. S. Aigrot: nothing to disclose
Valentina Mazziotti: nothing to disclose
C. Lubetzki: nothing to disclose
A. Desmazières: nothing to disclose