Abstract
The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants.
Highlights
Among all sensory systems, only olfaction can be modulated at the peripheral level by neuronal survival as only olfactory sensory neurons (OSNs) are renewed throughout the lifetime of the animal (Graziadei, 1973)
INTRANASAL TREATMENT WITH ENDOTHELIN RECEPTOR ANTAGONISTS INCREASED APOPTOSIS IN THE OE AND REDUCED THE OSN RESPONSES TO ODORANTS We had previously shown that endothelin acts as an antiapoptotic factor for olfactory epithelium cells in vitro (Laziz et al, 2011)
We evaluated the level of apoptosis by TUNEL quantification between control and treated pups (BQ) in the dorso-medial area of the OE
Summary
Only olfaction can be modulated at the peripheral level by neuronal survival as only olfactory sensory neurons (OSNs) are renewed throughout the lifetime of the animal (Graziadei, 1973). As OSNs are in direct contact with the environment, they are under permanent aggression from oxidative stress, pathogens or xenobiotics and have a limited life expectancy. They regularly undergo apoptosis and are renewed from basal cells (Schwob, 2002). It has been clearly demonstrated that the olfactory epithelium (OE) expresses antiapoptotic factors affecting OSNs (Moon et al, 2009) but the existence of activity-dependant survival of OSNs has remained controversial. It clearly shows that the environment modulates OSN life span with olfactory receptor (OR) specificity (Rimbault et al, 2009; He et al, 2012; Zhao et al, 2013). The controversy in literature dealing with activity dependent OSN survival remains to be addressed
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