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The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo
Published on: October 30, 2014
Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell
Sara Nocentini1, Diego Reginensi, Simón Garcia
1Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia, Barcelona Science Park, University of Barcelona, Barcelona, Spain.
Abstract:
Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but instead a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion, and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo receptor complex and that their migration is blocked by myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over myelin. Our data relate the decrease of traction force of OEC with lower migratory capacity over myelin, which correlates with changes in the F-actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo receptor inhibitor NEP1-40.
Insights
Olfactory ensheathing cells (OECs) are crucial for nerve repair. Myelin inhibits OEC migration by reducing their traction force, but this can be overcome using Nogo receptor inhibitors.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Olfactory receptor axons grow from the peripheral to the central nervous system, guided by olfactory ensheathing cells (OECs).
- OEC transplantation is a promising therapy for spinal cord injuries and neural diseases, but OECs are functionally heterogeneous.
- OEC migration is influenced by inhibitory molecules and chemical gradients, impacting their therapeutic potential.
Purpose of the Study:
- To investigate the effect of myelin on rodent OEC migration and mechanical properties.
- To determine the role of the Nogo receptor complex in OEC migration over myelin.
- To explore therapeutic strategies for enhancing OEC migration using Nogo receptor inhibition.
Main Methods:
- Assessment of Nogo receptor complex component expression in rodent OECs.
- Cell tracking and traction force microscopy to analyze OEC migration and mechanical properties on myelin.
- Evaluation of F-actin cytoskeleton and focal adhesion distribution during OEC migration.
- Treatment of OECs with the Nogo receptor inhibitor NEP1-40.
Main Results:
- Rodent OECs express all components of the Nogo receptor complex and their migration is inhibited by myelin.
- OEC migration over myelin is associated with decreased traction force, altered F-actin cytoskeleton, and focal adhesion distribution.
- Incubation with the Nogo receptor inhibitor NEP1-40 enhanced OEC traction force and migratory capacity.
Conclusions:
- Myelin inhibits OEC migration by reducing their traction force, mediated by the Nogo receptor complex.
- Targeting the Nogo receptor pathway with inhibitors like NEP1-40 can enhance OEC migration.
- These findings have implications for improving OEC-based therapies for spinal cord injury and other neurological disorders.
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