Olfactory pathway plasticity, early response of olfactory ensheathing cells and microglial cells to a massive damage of the olfactory epithelium

LUIS ERNESTO ACOSTA; CHARLES A. GREER; DIEGO RODRÍGUEZ GIL; LORENA RELA

Carry-le-Rouet

Congreso; 23rd Meeting of the French Glial Cell Club; 2016

Marseille University

The primary olfactory pathway is formed by the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Olfactory sensory neurons (OSNs) are generated throughout life and they extend an axon from the olfactory epithelium of the nasal cavity to the olfactory bulb in the central nervous system. The olfactory nerve is unique among peripheral nerves, because new OSN axons reinnervate the central nervous system after ablation restoring function and topographic organization. It has been proposed that the olfactory nerve is permissive for axon outgrowth due to the presence of a unique population of glia: the olfactory ensheathing cells (OECs).These specialized glial cells accompany the axons of OSNs from the epithelium to the olfactory bulb. Nonetheless, OECs share some properties with astrocytes, Schwann cells, oligodendrocytes and radial glial cells. We hypothesize that the plasticity and regenerative capacity of the olfactory nerve after damage is associated with an upregulation of stem cell proliferation within the olfactory nerve leading to the differentiation of OECs that then accompany the extending axons from newly generated OSNs. The identification of mechanisms that regulate OEC response to damage will be relevant for understanding the regenerative capacity of the olfactory system and essential to optimizing strategies using OEC transplants as a therapeutic approach to treat traumatic injury or degenerative diseases of the nervous system.To test the hypothesis that the plasticity and regenerative capacity of the olfactory nerve after damage is associated with an upregulation of stem cell proliferation within the olfactory nerve we used an experimental approach that induces degeneration-regeneration of OSNs in mice with one intraperitoneal injection of the olfatotoxin methimazole (75 mg/kg) on day 0. To detect proliferation of different cohorts of cells we injected thymidine analogs that are incorporated into the DNA of proliferating cells and can be later revealed by immunostaining at day 1 and 4. The olfactory tissue was collected at days 4, 14 and 30 post-lesion to evaluate proliferation at different stages of the degeneration-regeneration process.We found that OECs do not respond with early proliferating events as a consequence of damage. Nevertheless, they respond by modifying their anatomical distribution into different layers of the olfactory bulb. We also found that the response of microglial cells involved events of proliferation and that these cohorts of cells decreased in number with time. This decrease could be explained by either dilution of the thymidine analogs as a consequence of proliferation, by cell death of microglial cells or by a combination of both.