Poster Presentation 6th Australian Health and Medical Research Congress 2012

Effects on adult olfactory stem cells following the X-ray irradiation of the mouse olfactory neuroepithelium (#385)

Carla Cunha 1 , Yvonne Hort 1 , John Shine 1 , Kharen L Doyle 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

The olfactory neuroepithelium lines the upper nasal cavity and is in direct contact with the external environment and the olfactory bulbs. The ability to self-renew throughout life and the reproducible recovery after injury make it a model tissue to study mechanisms underlying neurogenesis. In this study, X-rays were used to disrupt proliferating olfactory stem cell populations and to assess their role in the cellular and morphological changes involved in olfactory neurogenic processes.

Mice at 8 weeks of age were anaesthetised (75 mg/kg Ketamine/15 mg/kg Xylazine) prior to their nose being exposed to 8Gy of X-rays (the rest of their body was protected with a lead shield). We subsequently analysed the histological and functional effects of this dose of X-rays on the olfactory neuroepithelium at 2 hours, 24 hours, 1 week, 2weeks and 5 weeks. We have shown an immediate cessation of proliferating olfactory stem cells as demonstrated by BrdU, Ki67 and pH3 expression. At 1 and 2 weeks there was an increase in the neural transcription factors Mash1 and Pax6 expression, as well as a disruption of the basal lamina and increase in glandular cell marker expression. Coincident with these changes was an impairment of the olfactory function in vivo using the Buried Food Pellet and the Habituation/Dishabituation tests. Overall, we have shown significant changes in basal olfactory stem cell proliferation as well as morphological changes in the olfactory neuroepithelium following X-ray irradiation. There is also involvement of the basal lamina as well as a clear role for glandular and sustentacular cells.