Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

No abstract

Background: It remains unclear whether the metabolic activity of nasal mucus in the olfactory and respiratory areas is different. Moreover, age-and olfactionrelated changes may affect metabolism.Methods: Hexanal, octanal, and 2-methylbutanal were selected for in vitro metabolism analysis and compared between the olfactory cleft and respiratory mucus of participants < 50-year-old with normal olfaction using gas chromatography mass spectrometry. The metabolic activity of hexanal in the olfactory cleft mucus was further compared between three groups, (1) normal olfaction, age < 50 years old, (2) normal olfaction, age ≥50 years old, and (3) idiopathic olfactory impairment. To characterize the enzyme(s) responsible for aldehyde reduction, we also tested if epalr22897estat and 3,5-dichlorosalicylic acid, types of reductase inhibitors, affect metabolism.Results: Conversion of aldehydes to their corresponding alcohols was observed in the olfactory cleft and respiratory mucus. The metabolic production of hexanol, octanol, and 2-methybutanol was significantly higher in the olfactory cleft mucus than in the respiratory mucus (p < 0.01). The metabolic conversion of hexanal to hexanol in the mucus of the idiopathic olfactory impairment group was significantly lower than that in the age-matched normal olfaction group. Excluding the nicotinamide adenine dinucleotide phosphate (NADPH) regenerating system from the reaction mixture inhibited metabolism. The addition of either epalr22897estat or 3,5-dichlorosalicylic acid did not inhibit this metabolic conversion. Conclusions:The enzymatic metabolism of odorants in the olfactory cleft mucus is markedly higher than in the respiratory mucus and decreases in patients with idiopathic olfactory impairment.

Background: The incidence of olfactory impairment increases with age; however, the detailed molecular and cellular mechanisms underlying this increase are yet to be determined.Methods: We examined the influence of aging on olfactory receptor neurons (ORNs), which are maintained by a unique stem cell system, from olfactory progenitor cells to mature ORNs, by histological comparisons of the physiological status of the olfactory epithelium between young adult and aged mice. Furthermore, we clarified the expression of genes encoding inflammatory cytokines, neurotrophins, growth factors, and extracellular matrix proteins to reveal the molecular mechanisms underlying olfactory impairment caused by aging.Results: The numbers of mature and immature ORNs, but not olfactory progenitors, decreased in the aged olfactory epithelium, with a concurrent reduction in Ki-67-positive proliferating cells. Transcriptome analyses revealed an increase in Il6, encoding a component of senescence-associated secretary phenotypes (SASP), and a decrease in Igf1, encoding a growth factor for ORNs, in the aged nasal mucosa. Interestingly, expression levels of several extracellular matrix genes, including Col1a2, decreased in the aged nasal mucosa. Consistent with the transcriptional changes, the number of Col1a2-GFP-positive cells decreased in the aged lamina propria.Conclusions: Our data suggest that reduction in ORN number and cell proliferation, reduced extracellular matrix gene expression, and increased SASP contribute to olfactory impairment during aging.

Carotid body tumors (CBTs) are rare neoplasms of the carotid body. Most CBTs are benign; however, some can show malignant behavior. Malignant CBTs have an unpredictable history; often, there is no correlation between the histologic findings and the clinical behavior. They are usually diagnosed by the development of local recurrence or lymph node metastasis following total resection of the primary mass, or by the detection of distant metastasis. There are few reports of histopathologic confirmation of malignant CBTs. We report a rare case of malignant CBT with distant metastases, in which the diagnosis was confirmed by histopathology, and present a review of the literature.