Kinetic Effects of Heat Stress on Olfaction: A Thermodynamic Evaluation of Electrical Responses to Odorants in Olfactory Epithelia
Type of DegreePhD Dissertation
General Veterinary Medicine
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Detection dogs are exposed to some of the most extreme environmental conditions in the world while simultaneously expected to maintain maximal olfactory function. Sometimes these conditions exceed their thermoregulatory capabilities and cause permanent damage, or even death. Extreme heat stress has been shown to adversely affect the gastrointestinal tract, causing damage to the mucosa protecting the internal environment of the body from harmful bacteria and endotoxins. Dysfunction of this protective barrier increases intestinal permeability and diffusion of toxic bacterial components from the gut lumen into the blood. Growing evidence of olfactory receptor expression in various non-sensory organs has expanded our scope of olfactory system involvement beyond the nasal cavity. Additionally, these ectopic olfactory receptors have been shown to interact with microbial by-products, even playing important regulatory roles other than simply the sense of smell. Given the extensive interactions between the GI tract and central nervous system function, as well as the direct exposure of olfactory sensory neurons to the external environment, the adverse effects of heat stress on intestinal physiology may also occur within the olfactory system. Olfaction may be one of the many physiological functions affected by heat stress. Our goal is to investigate the effects of heat stress on olfactory function, including the effects of temperature on zinc nanoparticles, which we previously demonstrated to have strong enhancement of olfactory neuronal responses to odorant stimulation and are thought to play an important role in the initial events of olfaction. In this work, we examine the effects of both environmental and metabolic heat stress on the kinetic properties of rat olfactory sensory neurons ex vivo using electroolfactogram (EOG) recordings from dissected olfactory epithelium (OE). The electrical activity of olfactory epithelia in response to odorant stimulation was assessed. Exposing rats to heat stress conditions resulted in a kinetic shift in signal activation and deactivation, showing faster rise and decay response times. Exposing olfactory epithelia dissected from non-stressed rats to various temperatures resulted in a change in EOG response stability, amplitude, and calculated thermodynamic parameters with increasing temperatures. Additionally, zinc nanoparticle preparations exposed to high temperatures and long-term storage showed increased levels of oxidization, which inhibited their ability to enhance olfactory responses. A preservation technique using a polyethylene glycol coating (PEGylated) nanoparticles resulted in a resistance to temperature-induced oxidation and conserved the enhancement effects on olfactory function. Several conclusions were drawn regarding thermal challenge to olfactory epithelium. Thermodynamic properties at the epithelial surface were extrapolated from kinetic calculations, and processes associated with EOG responses are entropy driven. The large entropy values calculated from these experiments indicated a decrease in molecular rotational and translational degrees of freedom of the olfactory receptor binding pocket – potentially allowing easier access for ligand binding. Secondly, activation energy and enthalpy were found to be small with respect to entropy contribution and free energy. This suggests that the transition barrier is lowered through entropic and enthalpic contributions, referred to as “activation-less” binding of odorants to the olfactory receptor.