Apoptosis induced by prolonged exposure to odorants in cultured cells from rat olfactory epithelia

Arturo Prat University, Iquique, Tarapacá, Chile
Brain Research (Impact Factor: 2.84). 09/2006; 1103(1):114-22. DOI: 10.1016/j.brainres.2006.05.072
Source: PubMed


Multicellular organisms undergo programmed cell death (PCD) as a mechanism for tissue remodeling during development and tissue renewal throughout adult life. Overdose of some neuronal receptor agonists like glutamate can trigger a PCD process termed excitotoxicity in neurons of the central nervous system. Calcium has an important role in PCD processes, especially in excitotoxicity. Since the normal turnover of olfactory receptor neurons (ORNs) relies, at least in part, on an apoptotic mechanism and odor transduction in ORNs involves an increase in intracellular Ca2+ concentration ([Ca2+]i), we investigated the possibility that long-term exposures to odorants could trigger an excitotoxic process in olfactory epithelial cells (EC). We used single-cell [Ca2+]i determinations and fluorescence microscopy techniques to study the effects of sustained odorant exposures in olfactory EC in primary culture. Induction of PCD was evaluated successively by three independent criteria: (1) measurements of DNA fragmentation, (2) translocation of phosphatidylserine to the external leaflet of the plasma membrane, and (3) caspase-3 activation. Our results support the notion of an odorant-induced PCD in olfactory EC. This odorant-induced PCD was prevented by LY83583, an odorant response inhibitor, suggesting that ORNs are the main epithelial cell population undergoing odorant-induced PCD.

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Available from: Sebastian Brauchi, Mar 22, 2015
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    • "Those factors are coming partly from the OM, as neurons can survive for a long period after pharmacological olfactory bulb depletion (Sultan-Styne et al., 2009). In addition, odorant stimulation also modulates the survival of ORNs (Watt et al., 2004; Brauchi et al., 2006; Suh et al., 2006; Tian and Ma, 2008). "
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    • "Second, OSN death may be regulated by odorant exposure; under the theory that neuronal turnover provides a mechanism for plasticity, selective death would allow an organism to adapt to changes in a complex and dynamic olfactory environment. Unfortunately, effects of odorant stimulation on survival have been mixed: while one group found a selective enhancement of survival of sensory neurons expressing an activated OR (Watt et al., 2004), a more recent study demonstrated that prolonged odorant exposure induces excitotoxic OSN death in culture after only 3 hours (Brauchi et al., 2006). Thus, it seems likely that the ongoing death of OSNs in the adult brain is intrinsically programmed; defining the mechanism of this form of programmed cell death would therefore be of interest. "
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