Development of fish cell lines for use in ecotoxicology and fish health: the case for fish olfactory cells

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The sense of smell or olfaction is critical for fish to feed, migrate, reproduce and/or escape predation but could be impaired by environmental contaminants. The cells responsible for olfaction are olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). The OE is the outer layer of the olfactory mucosa (OM) folded as rosettes within the nasal cavity. OSNs contain odour receptors and upon detecting odours, send signals through axons to the olfactory bulb from where they get processed and relayed to other brain regions. The OE can be considered the environmental-brain interface, with the environment being water for fish and air for humans. Therefore, the fish OE is readily exposed to toxicants and pathogens in water. I am proposing to develop fish olfactory cell cultures, including continuous or immortal cell lines, so that they can be used in basic and applied research on the OM. Cell cultures allow researchers to do experiments on simplified systems in which cellular inputs are better controlled and outputs are more easily read, leading to more interpretable results. Continuous cell lines have the additional advantages of permitting research without using animals (fulfilling a societal desire to reduce animal use in research), of making possible studies on fish that are endangered or difficult to maintain in the lab, and of providing an unlimited supply of cells from tissues that may be too small to study otherwise. Although OSNs have the odorant receptor proteins, other OM cell types are also important because they support the continuous production of OSNs, which is necessary because OSNs are constantly dying and renewing. In addition to OSN cultures, I will try to get cell lines of stem and progenitor cells that give rise to OSNs and of supporting cells (SCs) in the OE and of olfactory ensheathing cells (OECs) that protect and guide the OSN axons. Leucocyte cultures from the lamina propria will also be sought. An applied use of fish OM cultures could be to help improve development of intranasal vaccines for fish aquaculture in the future.For now, I am proposing to use these cell cultures to study an emerging class of environmental contaminants: neonicotinoids (NNs). NNs are currently the most commonly used insecticides but because of their wide use, and water being the ultimate sink, NNs might have off-target actions on fish. Any detrimental actions of NNs on the olfactory cells could have implications for fish behaviour and the health of fish populations in the wild, especially for migrating salmonids that depend heavily on olfaction. Understanding detrimental actions of environmental contaminants on the OM could also have implications for human health. Olfactory system dysfunction has been implicated in several human medical conditions, including schizophrenia, Alzheimer's and autism, and comparative cellular models could contribute to the understanding and treatment of these complex disorders.