Changes In Olfactory Epithelium Research Articles

Reduced amount of olfactory receptor neurons in the rat model of depression

Reduced olfactory sensitivity has been reported in depressive disorder. However, the pathological mechanism is still unclear. The reduced olfactory bulb (OB) volume and reduced hippocampal neurogenesis has been unraveled in major depressive disorder (MDD). However, changes in olfactory epithelium (OE) have not been reported, which might contribute to olfactory deficits in MDD. In the context, we investigated the thickness of OE in a chronic unpredictable mild stress (CUMS) rat model of depression using hematoxylin and eosin (HE) staining. Simultaneously, the basal cells (labeled by nerve growth factor receptor (p75NGFR)), immature olfactory receptor neurons (ORNs) (marked by growth-associated protein 43 (GAP43)) and mature ORNs (labeled by olfactory marker protein (OMP)) in OE were detected by immunohistochemistry. The results showed that the thickness of OE, the number of basal cells, immature ORNs as well as mature ORNs decreased dramatically in the OE of CUMS rats. Those findings indicate that the reduced number of ORNs might induce OE atrophy in CUMS rats and the abnormalities of the OE may be partially responsible for the reduced olfactory sensitivity in MDD.

Investigation of Initial Changes in the Mouse Olfactory Epithelium Following a Single Intravenous Injection of Vincristine Sulphate

To investigate initial changes in the olfactory epithelium, vincristine sulphate (VCR) was administered intravenously once to male BALB/c mice on day 1 in comparison with unilateral bulbectomy (UBT). The light and electron microscopy of the olfactory epithelium, nerve and/or bulb with BrdU-morphometry was performed sequentially. Further, whole-body radioluminography was conducted at 1 and 24 hours postdose. Apoptosis and an increased number of mitotic cells with a tendency toward decreasing BrdU-positive olfactory epithelial cell counts were observed in olfactory epithelial cells at 6 hours postdose of VCR and became more pronounced at 24 hours postdose. These changes disappeared on days 4 or 15, but minimal axonal degeneration was seen in the olfactory nerve from day 4 onward. Semiquantitative measurement of VCR levels in the ethmoturbinals elicited high drug retention even 24 hours after administration. In contrast, UBT showed no effect on mitosis and BrdU-positive cell counts at 6 hours postdose, but severe lesions in the olfactory epithelium and nerve were seen on days 2, 4, and/or 15. The above results suggest that the initial event of VCR-induced apoptosis in the mouse olfactory epithelium would be mitotic arrest with high drug retention, unlike that evoked by UBT.

Cell death of olfactory receptor neurons in a rat with nasosinusitis infected artificially with Staphylococcus.

Nasosinusitis is a common cause of acquired hyposmia or anosmia. To study the apoptotic death of olfactory receptor neurons in nasosinusitis, we made an inflammation model in rat infected with Staphylococcus. The histochemical changes in olfactory epithelium were examined using antibodies against protein gene product 9.5 (PGP 9.5), single-strand DNA (ssDNA), Bcl-2 and Bax that might be involved in the apoptosis of olfactory receptor neurons. The thickness of olfactory epithelium and the number of ssDNA-labeled cells were evaluated in each post-treatment group and the results were analyzed by two-way analysis of variance (ANOVA) and post hoc tests. Hematoxylin-eosin staining showed that a severe inflammatory reaction had occurred on the infected side of the nasal cavity and sinus, but not on the non-infected side. However, apoptosis of olfactory receptor neurons occurred on both sides; the apoptosis on the non-infected side started later and behaved like a shadow curve similarly to the infected side. Repeated measures ANOVA showed significant differences of both the thickness of olfactory epithelium (P < 0.0001) and the number of ssDNA-labeled cells (P = 0.0339) in the epithelium between the infected side and non-infected side comparing treatment, time and their interactions. Bcl-2 and Bax were detected only on the infected side in the early stages. Thus, nasosinusitis induced the apoptosis of olfactory receptor neurons. However, the apoptosis occurred not only on the infected side, but also on the non-infected side with no significant inflammation. The Bcl-2/Bax family seems to play an important role in the apoptosis induced by infection, but not in the apoptosis on the non-infected side. The results suggest that mechanisms of apoptosis of olfactory receptor neurons on the infected side may differ from those on the non-infected side.

Olfaction and peripheral olfactory connections in methimazole-treated rats

Methimazole has been reported to produce extensive degenerative changes in olfactory epithelium and a severe deficit in odor detection [Genter BM, Owens DM, Carlone HB, Crofton KM. Fundam. Appl. Toxicol. 1996;29:71–77; Genter BM, Owens DM, Deamer NJ, Blake BL, Wesley DS, Levi PE. Toxicol. Pathol. 1995;23:477–486.]. To examine this further, rats were tested on olfactory detection and discrimination problems before and after intraperitoneal injection of 300 mg/kg methimazole. In the first 2 days after treatment, experimental rats had nasal congestion and a modest decrement on odor detection and odor mixture discrimination tasks. They performed almost as well as control rats on the third post injection day. In a separate group of rats, anterograde transport of horseradish peroxidase from olfactory epithelium to the bulb was examined 1, 2, 3, and 5 days after administration of methimazole. The treatment produced a modest but progressive disruption of bulbar input: 2 days after administration only approximately 10% of bulbar glomeruli had reduced levels of reaction product while 30–40% of glomeruli had little or no reaction product in 3–5 day survival rats. These results indicate that methimazole is not a particularly effective olfactotoxin and does not produce anosmia or even a severe hyposmia.

An ultrastructural study of age-related changes in mouse olfactory epithelium.

Transmission and scanning electron microscopic examinations were undertaken to detail changes in the olfactory epithelium (OE) resulting from the ageing process. Samples were prepared from 3% glutaraldehyde/1% formaldehyde perfused mice aged 6 months and 29-30 months. Compared to OE from young adults, a number of striking changes were apparent in tissue from older animals. The most obvious of these were extensive local accumulations of large inclusion bodies, totally disrupting the normal morphology of such affected areas of olfactory epithelium. Even in areas where these deposits were absent, other significant signs of ageing were noted in the seemingly unaffected OE of all older mice studied. Quantitative analysis of semi-thin resin sections revealed that the OE of aged mice was significantly reduced in thickness, and with significantly fewer olfactory sensory neurons, irrespective of whether or not inclusions were present. In addition, pale cells, which have been suggested to be a form of degenerating cells, were more abundant in aged OE. The straight, sharp boundary between respiratory and olfactory epithelia which is seen in young adults became irregular and disrupted with age due to an intermingling of the respiratory and olfactory cells. Such structural alterations may parallel olfactory dysfunction reputed to occur in older mammals.

Structural and functional links between olfactory and reproductive systems: puberty-related changes in olfactory epithelium

The structural and functional link between olfactory and reproductive systems in male and female platyfish ( Xiphophorus maculatus) is demonstrated by the connection of receptors in the nasal epithelium to a center in the brain that has a primary role in the development and functioning of the reproductive system. Profound morphological changes occur in the nasal epithelium, and LH-RH content increases in tracts of the olfactory lobe, at specific stages of sexual maturation and not according to chronological age. Our study provides new insight into the development of the mechanisms by which chemical environmental cues are received.