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An approach to address the effects of microglia depletion on degeneration and regeneration after olfactory nerve damage

Diego Martín Topsakalian

  • Ciudad Autónoma de Buenos Aires,
  • Argentina
  • Diego M. Topsakalian ¹
  • , Luis E. Acosta ¹
  • , Ana P. Piantanida ¹
  • , Jesica N. Unger ¹
  • , Juan E. Belforte ¹
  • , Lorena Rela ¹
  • 1 IFIBIO Houssay (CONICET- UBA)

Olfactory ensheathing glia is recognized for its ability to promote axonal growth, a property that is normally used to explain the regenerative capacity of the olfactory nerve. However, little attention has been paid to the possibility that immune cells (microglia/macrophages) present in the afferent olfactory pathway participate in its repair, although they show signs of activation after damage. To determine whether microglial cells present in the afferent olfactory pathway mediate damage severity and/or recovery, we propose to analyze the effects of microglia depletion by PLX5622 in a mouse model of damage to the olfactory nerve by the olfactotoxin methimazole. The functional status of the olfactory nerve will be evaluated by a habituation/dishabituation olfactory test at four or fourteen days after damage. In addition, the same day of the behavioral test, we will collect tissue to obtain an anatomical correlate from histological preparations of the bulb and olfactory mucosa, to verify the microglial depletion and to evaluate the sensory neuron integrity. If microglial cells play a role in damage severity and/or resolution, we expect that the animals show partially conserved olfactory function or slower recovery, respectively, with PLX5622 treatment. This approach sets the basis to analyze whether inflammation modulates the neurotrophic properties of olfactory ensheathing cells.