Function Of Olfactory Neurons Research Articles

Dietary Approach for Post-COVID Treatment of Olfactory Loss

The spread of severe acute respiratory syndrome coronavirus [SARS-CoV-2] has consequently led to the global COVID-19 pandemic. Many patients, whether hospitalized or not, have reported a variety of complications that persist after recovery. The admission for COVID-19 has been associated with anosmia and hyposmia, the inability or decreased ability to smell. Deficiencies in the ability to smell tend to recover within weeks. However, a significant number of cases have been reported in which smell distortions last for several months. Experimental research has identified inflammation as a factor disrupting olfactory neurons. Precisely, local inflammation through cytokine release in sustentacular and horizontal basal cells interferes with the function of olfactory neurons. Further studies have reported that these local inflammatory events are not responsive to common corticoid treatments. Therefore, in order to mediate the recovery of olfaction in COVID-19 patients after viral recovery, this study evaluates vitamin C, vitamin D, vitamin E, and omega-3 polyunsaturated fatty acids to develop a prospective dietary approach with anti-inflammatory properties to reduce the local inflammation of sustentacular and horizontal basal cells.

Effect of gut microbes on olfactory behavior of Drosophila melanogaster larva.

The symbiotic relationship between an animal and its gut microbiota is known to influence host neural function and behavior. The mechanisms by which gut microbiota influence brain function are not well understood. This study measures the impact of gut microbiota on olfactory behavior of Drosophila larvae and explores possible mechanisms by which gut microbiota communicate with neural circuits. The microbiota load in Drosophila larvae was altered by treating them with antibiotics or probiotics. Control larvae and larvae with altered microbiota loads were subjected to olfactory assays to analyze the chemotaxis response of larvae to odorants. Larvae treated with antibiotics had reduced microbiota load and exhibited reduced chemotaxis response toward odorants compared to control animals. This behavioral phenotype was partially rescued in larvae treated with probiotics that resulted in partial recovery of microbiota loads. Expression levels of several olfactory genes in larvae subjected to different treatments were analyzed. The results suggest that the expression of certain components of the GABA signaling pathway is sensitive to microbiota load. The study concludes that the microbiota influences homeostatic mechanisms in the host that control GABA production and GABA-receptor expression, which are known to impact host olfactory behavior. These results have implications for understanding the bidirectional communication between a host organism and its microbiota as well as for understanding the modulation of olfactory neuron function.

Olfactory and middle meatal cytokine levels correlate with olfactory function in chronic rhinosinusitis.

The etiology of chronic rhinosinusitis (CRS)-associated olfactory loss is unclear, but may result from inflammatory changes in the olfactory epithelium that result in signaling dysfunction or loss of olfactory neurons. Several proinflammatory cytokines have been associated with CRS, but their expression within the olfactory cleft microenvironment and association with olfactory function is unknown. Prospective case-control study. Mucus was collected from the olfactory cleft and middle meatus of 31 CRS without nasal polyps subjects, 36 CRS with nasal polyps (CRSwNP) subjects, and 12 healthy controls. Olfactory function was assessed using the validated Smell Identification Test (SIT). Site-specific levels of 14 cytokines/chemokines (interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, tumor necrosis factor-α, Eotaxin, RANTES [regulated on activation, normal T cell expressed and secreted]) were assessed using a multiplex flow cytometric bead assay and correlated with SIT scores. Mucus cytokine levels in the olfactory cleft were strongly or moderately correlated with levels in the middle meatus for all but one measured inflammatory mediators. SIT scores were inversely correlated with levels of IL-2 (P = .006), IL-5 (P < .0001), IL-6 (P = .0009), IL-10 (P < .0001), and IL-13 (P < .0001), with significance largely driven by CRSwNP patients. The inflammatory microenvironment within the olfactory cleft mirrors that within the middle meatus. Elevated levels of IL-2, IL-5, IL-6, IL-10, and IL-13 in olfactory cleft mucus are associated with reduced olfactory identification scores in CRS patients. Altered levels of select olfactory mucus cytokines could potentially have deleterious effects on olfactory neuron function and turnover. NA. Laryngoscope, 128:E304-E310, 2018.

Interferon gamma causes olfactory dysfunction without concomitant neuroepithelial damage

Olfactory loss is a debilitating symptom of chronic rhinosinusitis (CRS). The pathophysiology of inflammatory olfactory dysfunction likely involves both conductive and sensorineural components. To study the interaction of CRS-associated inflammatory cytokines with the olfactory epithelium (OE), a transgenic mouse model was developed that allows temporally-controlled local gene expression. Interferon-gamma (IFN-γ) is a prototypical T helper 1 (Th1) cytokine linked to nonpolypoid CRS (CRSsNP), as well as sinonasal viral and bacterial infections. In this study, the effects of chronic IFN-γ expression on olfactory histology and function were investigated. IFN-γ secretion by olfactory sustentacular cells was induced in the transgenic mouse. Viability and gross behavior were unaffected. Mice were euthanized after 6 weeks of IFN-γ expression, and olfactory tissue was studied by histology, immunohistochemistry, and electro-olfactography (EOG). Findings were compared with uninduced littermates. IFN-γ expression did not result in alteration of the normal histologic architecture of the neuroepithelium or lamina propria. However, EOG recordings demonstrated a significant decrease in odorant responses after IFN-γ expression. In addition, a marked increase in submucosal CD45-positive cells was observed, the majority of which were CD3-positive and CD4-positive lymphocytes. Chronic IFN-γ expression in the mouse OE results in diminished odorant responsiveness, despite the absence of inflammatory tissue damage. This suggests a direct effect of IFN-γ on olfactory neuron function that may underlie olfactory loss in CRSsNP or viral infections. The infiltration of submucosal lymphocytes raises the possibility that other downstream cytokines also contribute to olfactory dysfunction.

Gonadotropin‐releasing hormone modulates voltage‐activated sodium current and odor responses in Necturus maculosus olfactory sensory neurons

The terminal nerve (nervus terminalis) extends from the basal forebrain to the nasal cavity and has been shown to contain gonadotropin-releasing hormone (GnRH). The specific function of the terminal nerve is unknown, but it has been hypothesized that it modulates the function of olfactory neurons. To examine the effects of GnRH on isolated Necturus maculosus olfactory sensory neurons (OSNs), we used the perforated configuration of the patch clamp technique to record current responses. GnRH had no effect on the membrane current at any holding potential but did modulate voltage-activated TTX-sensitive sodium current (INa). Within 1 min of applying GnRH, approximately 60% of the OSNs showed a decrease in the magnitude of INa. Initial responses to GnRH were inhibitory, although in one group of cells the initial inhibitory response was followed by a potentiation of INa with continual application (approximately 5 min). The time course of the GnRH response suggested that a second messenger pathway mediated the response. Inhibitors of PKC, tyrosine kinase, and PI3K were all able to inhibit the INa, but none of them could prevent the GnRH response. Application of a cAMP analog mimicked the effects of GnRH, and only inhibitors of PKA and PKG could prevent GnRH-induced inhibition of INa. This suggests that the modulation of voltage-activated sodium currents by GnRH involve a cyclic nucleotide pathway. In addition, GnRH modulated the odor responses of OSNs. Our data suggest the release of GnRH, presumably from the terminal nerve, can serve to modulate olfactory sensory neurons.

Development of Transgenic Mouse Models for the Study of Human Olfactory Dysfunction

Olfactory loss is a significant health problem that remains incompletely understood. The development of suitable animal models is essential to the progress of human olfactory loss research. Recent advancements in transgenic technology allow the creation of model systems to address causes of olfactory neuron dysfunction. This review describes two transgenic mouse models with potential usefulness in the study of olfactory loss and highlights the molecular techniques that underlie the development of such systems. Genetic constructs generated using standard molecular biological techniques are introduced into mouse germ lines either by homologous recombination or by random integration. One construct (UbI7) places the olfactory receptor I7 under control of the olfactory marker protein promoter. The other two constructs (TI) act together to direct expression of cytokines in the olfactory epithelium, creating a novel approach to the study of inflammatory olfactory loss. Powerful scientific tools now exist to develop animal models useful to the study of human olfactory disease. Transgenic olfactory neurons from the UbI7 mouse strain will respond to known odorants, facilitating experiments that examine in vitro modulation of olfactory neuron function. The ability to express specific genes in the olfactory mucosa of the TI mouse has great potential in elucidating the role of cytokines in the development of olfactory dysfunction in vivo.