Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well as molecular deficiencies such as punctual mutation in Disrupted‑in‑Schizophrenia 1 protein. In this regard, it is essential to understand the underlying molecular disturbances to determine the pathophysiological mechanisms of the disease. The signaling pathways activated by G protein‑coupled receptors (GPCRs) are key molecular signaling pathways altered in SZ. Convenient models need to be designed and validated to study these processes and mechanisms at the cellular level. Cultured olfactory stem cells are used to investigate neural molecular and cellular alterations related to the pathophysiology of SZ. Multipotent human olfactory stem cells are undifferentiated and express GPCRs involved in numerous physiological functions such as proliferation, differentiation and bioenergetics. The use of olfactory stem cells obtained from patients with SZ may identify alterations in GPCR signaling that underlie dysfunctional processes in both undifferentiated and specialized neurons or derived neuroglia. The present review aimed to analyze the role of GPCRs and their signaling in the pathophysiology of SZ. Culture of olfactory epithelial cells constitutes a suitable model to study SZ and other psychiatric disorders at the cellular level.

The pathological changes of Alzheimer\'s disease (AD) begin 10-20 years before clinical onset, and it is therefore desirable to identify effective methods for early diagnosis. The nasal mucosa is a target tissue for measuring AD-related biomarkers because the olfactory nerve is the only cranial nerve that is exposed to the external environment. We describe an autopsy case of rapidly advanced juvenile AD (JAD), focusing on the olfactory system. The formation of senile plaques, neurofibrillary tangles (NFTs), and neuropil threads was examined in the temporal cortex, hippocampus, olfactory bulb, and olfactory and respiratory epithelia in the bilateral olfactory clefts. Neurodegenerative changes in the olfactory and respiratory epithelia and the pathological deposition of amyloid β42 (Aβ42) and phosphorylated tau were also examined. As a result, senile plaques, NFTs, and neuropil threads were found in the temporal cortex, hippocampus, and olfactory bulb. NFTs were also found in the olfactory epithelium. Degenerated olfactory cells and their axons stained positive for phosphorylated tau. Supporting cells in the degenerated olfactory epithelium stained positive for Aβ42. In conclusion, pathological biomarkers of AD were expressed in the degenerated olfactory epithelium of this JAD patient. This observation suggests that nasal samples may be useful for the diagnosis of AD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause long-lasting anosmia, but the impact of SARS-CoV-2 infection, which can spread to the nasal cavity via the oral route, on the olfactory receptor neuron (ORN) lineage and olfactory bulb (OB) remains undetermined. Using Syrian hamsters, we explored whether oral SARS-CoV-2 inoculation can lead to nasal viral infection, examined how SARS-CoV-2 affects the ORN lineage by site, and investigated whether SARS-CoV-2 infection can spread to the OB and induce inflammation. On post-inoculation day 7, SARS-CoV-2 presence was confirmed in the lateral area (OCAM-positive) but not the nasal septum of NQO1-positive and OCAM-positive areas. The virus was observed partially infiltrating the olfactory epithelium, and ORN progenitor cells, immature ORNs, and mature ORNs were fewer than in controls. The virus was found in the olfactory nerve bundles to the OB, suggesting the nasal cavity as a route for SARS-CoV-2 brain infection. We demonstrated that transoral SARS-CoV-2 infection can spread from the nasal cavity to the central nervous system and the possibility of central olfactory dysfunction due to SARS-CoV-2 infection. The virus was localized at the infection site and could damage all ORN-lineage cells.

Background: Treatment of patients with anosmia is a major therapeutic challenge. The present study evaluated the efficacy of platelet-rich plasma (PRP) in the treatment of anosmia in patients with sinonasal polyposis. Methods:In the present clinical trial, atotal of 48 patients with sinonasal polyposis with theIran Smell Identification Test (I-SIT) score of <6 who completed the medical treatment and were observed 3 months after the sinus surgery were included and randomly divided in to 2groups. After endoscopic sinus surgery, the intranasal injection of 1 mL PRP and normal saline was performed in the olfactory region in the intervention and control groups, respectively. Odor function was assessed using the I-SIT at the baseline and at the end of the studyby an independent samples ttest. Results: Based on the findings of the present study, the I-SIT improved in both groups during the follow-up, as it reached from 2.63 ± 2.63 to 5.85 ± 2.46 after oral steroid administration and 18.93 ± 1.14 after surgery in the intervention group and from the baseline of 2.10 ± 2.83 to 5.62 ± 2.99 after receiving standard medical treatment and 18.43 ± 1.36in the control groupafter surgery. Although this improvement was significant in both groups in either time interval (all with p<0.001), there was no significant difference between the 2groups in terms of changes in the I-SIT score (p=0.802). Conclusion: According to the current study, PRP injection showed no short-term effect on the recovery of olfactory function in patients with sinonasal polyposis.

Olfactory sensory neurons (OSNs) of fish belong to three main types: ciliated olfactory sensory neurons (cOSNs), microvillous olfactory sensory neurons (mOSNs), and crypt cells. Mercury is a toxic metal harmful for olfaction. We exposed the olfactory epithelium of zebrafish to three sublethal Hg2+ concentrations. Molecular markers specific for the different types of OSNs were immunohistochemically detected. Image analysis of treated sections enabled counting of marked cells and measurement of staining optical density indicative of the response of OSNs to Hg2+ exposure. The three types of OSNs reacted to mercury in a different way. Image analysis revealed that mOSNs are more susceptible to Hg2+ exposure than cOSNs and crypt cell density decreases. Moreover, while the ratio between sensory/nonsensory epithelium areas is unchanged, epithelium thickness drops, and dividing cells increase in the basal layer of the olfactory epithelium. Cell death but also reduction of apical processes and marker expression could account for changes in OSN immunostaining. Also, the differential results between dorsal and ventral halves of the olfactory rosette could derive from different water flows inside the olfactory chamber or different subpopulations in OSNs.

The aim of this article is to present the research protocol for a prospective cohort study that will assess the olfactory function and the effect of an intervention based on olfactory training in healthy very old adults (≥75 years old). A convenience sample of 180 older people (50% female) will be recruited in three different environments: hospitalized control group (CH) with stable acute illness (n = 60); ambulatory control group (CA) of community-based living (n = 60); and an experimental odor training group (EOT) from nursing homes (n = 60). The odor training (OT) intervention will last 12 weeks. All the volunteers will be assessed at baseline; CA and EOT groups will also be assessed after 12 weeks. The primary end point will be change in olfactory capacity from baseline to 12 weeks period of intervention or control. The intervention effects will be assessed with the overall score achieved in Sniffin Sticks Test (SST) - Threshold, Discrimination, and Identification (TDI) extended version. Secondary end points will be changes in cognitive tasks, quality of life, mood, immune status, and functional capacity. All these measurements will be complemented with an immune fitness characterization and a deep proteome profiling of the olfactory epithelium (OE) cultured ex vivo. The current study will provide additional evidence to support the implementation of olfactory precision medicine and the development of immunomodulatory nasal therapies based on non-invasive procedures. The proposed intervention will also intend to increase the knowledge about the olfactory function in very elderly people, improve function and quality of life, and promote the recovery of the health.

The olfactory recess (OR) is a restricted space at the back of the nasal fossa in many mammals that is thought to improve olfactory function. Mammals that have an olfactory recess are usually described as keen-scented, while those that do not are typically thought of as less reliant on olfaction. However, the presence of an olfactory recess is not a binary trait. Many mammal families have members that vary substantially in the size and complexity of the olfactory recess. There is also variation in the amount of olfactory epithelium (OE) that is housed in the olfactory recess. Among New World leaf-nosed bats (family Phyllostomidae), species vary by over an order of magnitude in how much of their total OE lies within the OR. Does this variation relate to previously documented neuroanatomical proxies for olfactory reliance? Using data from 12 species of phyllostomid bats, we addressed the hypothesis that the amount of OE within the OR relates to a species\' dependence on olfaction, as measured by two commonly used neuroanatomical metrics, the size of the olfactory bulb, and the number of glomeruli in the olfactory bulb, which are the first processing units within the olfactory signal cascade. We found that the percentage of OE within the OR does not relate to either measure of olfactory \"ability.\" This suggests that olfactory reliance is not reflected in the size of the olfactory recess. We explore other roles that the olfactory recess may play.