Distribution and severity of spontaneous lesions in the neuroepithelium and Bowman’s glands in mouse olfactory mucosa: age-related progression

Abstract

Age-related changes were examined in the distribution and severity of spontaneous lesions in the neuroepithelium and Bowman's glands in mouse olfactory mucosa. The olfactory mucosa of female ICR mice at postnatal ages from 10 days to 16 months were investigated histologically by hematoxylin and eosin staining, high-iron diamine-Alcian blue (HID-AB) staining, and immunohistochemistry for olfactory marker protein (OMP), betaIII tubulin (betaIIIT), and Ki67. The lesions in the neuroepithelium and Bowman's glands were quantitatively assessed by morphometric analyses of sections stained with anti-OMP antibody or HID-AB. The first appearance of neuroepithelial abnormality was observed in the dorsomedial portion of the olfactory mucosa in 5-month-old mice. The distribution and severity of lesions progressed with increasing age. In mildly affected epithelium in which OMP-positive olfactory receptor neurons (ORNs) were present but in smaller amounts, the numbers of betaIIIT-positive and Ki67-positive neuroepithelial cells tended to be increased, indicating that neurogenesis was upregulated in these areas. In contrast, severely affected epithelium in which OMP-positive ORNs were virtually absent showed high variability in the numbers of betaIIIT- and Ki67-positive cells among the areas examined, probably reflecting differences in the capacity of the basal cells remaining in the affected area to generate new neuronal cells. Histological analysis with HID-AB revealed that spontaneous lesions in Bowman's glands also occurred in aged mouse olfactory mucosa. Lesions in the neuroepithelium and underlying Bowman's glands tended to be spatially co-localized, suggesting a close association between pathogeneses in these two structures. Moreover, lesions in Bowman's glands were associated with changes in the biochemical composition of mucus on the olfactory mucosa. This information should prove useful in improving the understanding of the pathogenetic mechanisms underlying age-related changes in the peripheral olfactory system.

Age‐related changes in cell dynamics of the postnatal mouse olfactory neuroepithelium: Cell proliferation, neuronal differentiation, and cell death

“…All procedures were approved by the University of Tokyo Animal Care Committee and carried out in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Although the mice in each age group appeared to be in good health at the time of sacrifice, we observed spontaneous age-related degenerative changes of the neuroepithelium in some parts of the 16-month-old olfactory mucosa, including an apparent reduction in the number of, or the total loss of, the OMP-positive neurons compared with age-matched normal-appearing olfactory mucosa, as described in our previous studies (Watanabe et al, 2006;Kondo et al, 2009) and those from other laboratories (Loo et al, 1996;Nagano et al, 1997;Rosli et al, 1999;Holbrook et al, 2005). Because the purpose of the present study was to obtain information regarding the age-related changes in cell dynamics under undisturbed conditions, we tried to eliminate the influence of such degenerative parts of the neuroepithelium on the analysis of cell dynamics.…”

“…The OMP antiserum (generously provided by Dr. Frank Margolis, University of Maryland) recognized a single band of 19 kD molecular weight corresponding to OMP on Western blots of mouse and rat olfactory bulb (Baker et al, 1989). It immunolabeled a cell population that had been morphologically classified as mature olfactory neurons in the rodent olfactory neuroepithelium in a number of previous reports (Verhaagen et al, 1989;Schwob et al, 1992;Kondo et al, 2009). According to the technical datasheet from Oxford Biotechnology, the BrdU antibody recognizes both BrdU in single-stranded DNA and BrdU attached to a protein carrier, as well as free BrdU.…”

“…Histological studies of the olfactory mucosa in laboratory animals such as mice and rats have shown an age-dependent decrease in neuroepithelial thickness (Walker et al, 1990;Weiler and Farbman, 1997;Watanabe et al, 2006). Spontaneous degenerative changes of the olfactory mucosa, including the loss of mature ORNs and the replacement of olfactory neuroepithelium by respiratory-like ciliated epithelium, progress both in terms of distribution and severity with increasing age (Nakashima et al, 1984;Trojanowski et al, 1991;Loo et al, 1996;Nagano et al, 1997;Rosli et al, 1999;Holbrook et al, 2005;Kondo et al, 2009). These agerelated structural changes in the olfactory neuroepithelium suggest that age could influence the parameters of cell dynamics that regulate neuronal population numbers, such as mitosis of the basal cells, differentiation of neuronal cells, and cell death.…”

Enzymatic Conversion of Odorants in Nasal Mucus Affects Olfactory Glomerular Activation Patterns and Odor Perception

“…Similarly, it is possible that the amount of odorant metabolizing enzymes in nasal mucus may vary depending on physiological conditions. Also, age-related progression of lesions has been observed in the Bowman's gland in olfactory mucosa (Kondo et al, 2009), which may affect the amount of mucosal enzymes. The expression levels of these enzymes may be different between races, as was found for aldehyde dehydrogenase (Chen et al, 1991).…”

Leptin-sensitive OBP-expressing mucous cells in rat olfactory epithelium: a novel target for olfaction-nutrition crosstalk?

“…Moreover, mutant mice defective in two subtypes of IP3 receptors predominantly expressed in the nasal glands display impaired nasal mucus secretion correlated to an elevation of the threshold for odorant sensitivity (Fukuda et al 2008). However, few data have demonstrated a direct link between mucus composition and olfactory performance through the control of odorant access to the receptor (Vidic et al 2008), genetic defects (Getchell et al 2006), or the age-related degeneration of BG (Kondo et al 2009) Surprisingly, the precise protein cartography of mucus composition has only been deciphered in humans (Debat et al 2007), and little is known about the nature of the molecules secreted by each type of gland in the rat. However, the major protein components of the olfactory mucus in mammals are the odorant-binding proteins (OBPs), which are members of the lipocalin family comprising OBP-I, OBP-II, and a variant of OBP-I, OBP-1f, in the rat (Briand et al 2000;Flower et al 1993;Pelosi 1994).…”