Morphological and behavioural changes occur following the X-ray irradiation of the adult mouse olfactory neuroepithelium

Abstract

BackgroundThe 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.ResultsWe have analysed the histological and functional effects of a sub-lethal dose of X-rays on the adult mouse olfactory neuroepithelium at 2 hours, 24 hours, 1 week, 2 weeks and 5 weeks. We have shown an immediate cessation of proliferating olfactory stem cells as shown by BrdU, Ki67 and pH3 expression. At 24 hours there was an increase in the neural transcription factors Mash1 and Pax6 expression, and a disruption of the basal lamina and increase in glandular cell marker expression at 1 week post-irradiation. Coincident with these changes was an impairment of the olfactory function in vivo.ConclusionsWe have shown significant changes in basal cell proliferation as well as morphological changes in the olfactory neuroepithelium following X-ray irradiation. There is involvement of the basal lamina as well as a clear role for glandular and sustentacular cells.

Effect of Radiation on Sucrose Detection Thresholds of Mice

“…Despite the olfactory controls in place, odor cues might have been used in part to perform the discrimination task in this study. If so, this would be more properly assessed by olfactory threshold testing as there is evidence that olfactory epithelium is susceptible to irradiation damage at the 8 Gy dose used in this experiment (Ophir et al 1988;Cunha et al 2012). The spike in threshold increases on day 11 also suggests there may be other mechanisms involving cell renewal which need further exploration.…”

Molecular and Neural Mechanism of Dysphagia Due to Cancer

“…There was no difference in apoptosis in the olfactory epithelium between the irradiation and control groups. Reduced neurogenesis, small olfactory bulbs, changes in the subtypes of the interneurons connecting the olfactory epithelium to the olfactory bulbs, and a significant reduction in GABAergic subtypes have been observed [72,73].…”

Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium

“…), then shielded with lead so that only their heads and necks would receive irradiation. Eight Gy of X-ray was administered by an RS 2000 Biological Irradiator (Rad Source Technologies, Inc.) in accordance with published studies that showed this amount of radiation induces changes in olfactory neuroepithelium without being lethal to the animals under study (Cunha et al 2012;Nguyen et al 2012). Because Cunha et al showed disruption in Bowman's glands and the basal lamina 1-week post 8 Gy irradiation, we chose this as our survival time point.…”

“…We did not observe any effects of radiation exposure on mucin expression at the 1-week time point. We selected a single 8 Gy dose because this has been shown to alter cellular function within mouse olfactory and taste mucosa without resulting in excess mortality (Cunha et al 2012;Nguyen et al 2012). At 1-week post irradiation, Cunha et al reported changes in mouse nasal mucosal morphology as well as olfactory performance as measured by behavioral testing.…”