Mouse Olfactory Epithelium Research Articles

Globosal basal cells are identified as proliferating cells in mouse olfactory epithelium.

Although anti-bromodeoxyuridine (BrdU) antibodies are used for detecting proliferating cells, they may stain proliferating cells in phases following the S-phase, except for G1. Anti-Ki67 antibodies are widely used for detecting proliferating cells in all phases of the cell cycle (G1-, S-, G2-, and M-phase), but not in resting cells (G0-phase). Anti-cyclin D1 antibodies are used to detect proliferating cells in the G1-phase. The present study investigated the olfactory epithelium of mice by double immunostaining using antibodies to BrdU, Ki67. cyclin D1, and cytokeratin 14 (CK14). The cells positive to the anti-BrdU antibody, the anti-Ki67 antibody, and the anti-cyclin D1 antibody differed from the cells positive to the anti-CK14 antibody. Thus, we confirmed that the proliferating cells in all the phases of the cell cycle, including the G1-phase, were globosal basal cells, which were the precursors of the olfactory cells.

Proliferation markers, proliferating cell nuclear antigen, Ki67, 5-bromo-2'-deoxyuridine, and cyclin D1 in mouse olfactory epithelium.

We immunohistochemically identified proliferating cells in the olfactory epithelium of mice, using an anti-proliferating cell nuclear antigen (PCNA) antibody, an anti-Ki67 antibody, an anti-5-bromo-2'-deoxyuridine (BrdU) antibody, and an anti-cyclin D antibody. Positive cells stained by the 4 antibodies were identified mainly in the basal layer. The mean numbers of positive cells stained by the 4 antibodies in 500 olfactory epithelium cells from each animal were as follows: PCNA-positive cells 42, Ki67-positive cells 23, BrdU-positive cells 13.7, and cyclin D1-positive cells 9.2. PCNA may be detected in both proliferating and resting cells. Ki67 is an intranuclear antigen expressed in proliferating, but not resting, cells. Anti-BrdU antibodies might stain proliferating cells only following the S-phase, but not the G1-phase. Cyclin D1 is a protein that works during the G1-phase of the cell cycle. When we stain proliferating cells using proliferating cell markers, it is important to consider the cell cycle phases during which each marker stains.

Mitogen-activated protein kinase phosphatase-1 in olfactory neural regeneration

Uniquely, olfactory neurons continuously replace themselves. Olfactory bulb ablation induces coordinated degeneration and regeneration in olfactory neuroepithelium; up-regulated growth factors bind to their receptors, initiating a phosphorylation cascade activating mitogen-activated protein kinases (MAPK). MAPK then relay proliferation signals to the nucleus. Mitogen-activated protein kinase phosphatase-1 (MKP-1) inactivates MAPK. We examined MKP-1 expression in adult mouse olfactory epithelium following bulbectomy using a reverse transcription-polymerase chain reaction (RT-PCR) as well as Western analysis. While MKP-1 expression was high in olfactory epithelium from control mice, it decreased greatly 2-3 weeks after bulbectomy in temporal association with increased tyrosine phosphorylation of MAPK. Thus, reduced MKP-1 expression may contribute to regeneration of olfactory neuroepithelium after bulbectomy via decreased dephosphorylation of MAPK.

Unusual regulation of cyclin D1 and cyclin-dependent kinases cdk2 and cdk4 during in vivo mitotic stimulation of olfactory neuron progenitors in adult mouse.

The molecular mechanisms underlying cell cycle control in neuronal progenitors have been investigated with adult mouse olfactory epithelium as a model system. Odor receptive neurons of mammalian olfactory epithelium are short-lived and renewed in the adult by mitotic division of intrinsic neuronal progenitors. Ablation of the synaptic target, olfactory bulb, induces sequentially extensive apoptosis of sensory neurons and then stimulation of progenitor proliferation, peaking at 36 h and 4 days, respectively, postlesion. Known molecular effectors of G1 phase entry have been assessed on protein extracts of olfactory organs sampled at various postbulbectomy times in adult mice. The decay of betaIII-tubulin and olfactory marker protein levels and the rise of proliferating cell nuclear antigen (PCNA) levels, starting 1 and 3 days, respectively, postlesion, provided the kinetic frame of neuronal dynamics. Cyclin D1, cyclin E, and cyclin-dependent kinase cdk2 levels, low in olfactory organ of intact mice, increased 3 days after bulbectomy in parallel with PCNA levels; cdk4 content was initially high and unaffected by lesioning. Western blots of the known cdk inhibitors revealed proliferation-related decreases of p18, p21, and p27 from high expression in intact organs. Immunoprecipitation of cdk2 and cdk4 fractions of protein extracts at 4 days postlesion (mitotic reaction peak) versus control, followed by cyclin D1 immunoblotting, and vice versa, revealed that levels of both cyclin D1/cdk2 and cyclin D1/cdk4 complexes, as well as their kinase activities, were dramatically increased after lesion. In vivo proliferation of olfactory neuronal lineage cells thus involves functional binding of cyclin D1 with cdk2 and cdk4, with differential activation mechanisms for cdk2 and cdk4. In addition, the RT-PCR-detected cyclin D1 mRNA level remained unaffected after bulbectomy, which indicated that the cyclin D1 rise should involve posttranscriptional mechanisms in this in vivo neuronal system. These observations are discussed, along with their relevance to cell cycle control and to olfactory neuron dynamics.

Olfactory epithelium consisting of supporting cells and horizontal basal cells in the posterior nasal cavity of mice.

The olfactory epithelium of mice generally consists of olfactory cells, progenitors of olfactory cells (globose basal cells), supporting cells, and horizontal basal cells. However, in the dorsal fossa (the roof) of the posterior nasal cavity of mice, we found seven epithelial patches consisting of only non-neuronal cell types, i.e., supporting cells and horizontal basal cells, among the normal olfactory epithelium. The supporting cells occupied three or four layers in the apical to middle regions; in the basal region, horizontal basal cells were localized in a single row adjacent to the basement membrane. Bowman's gland ducts were also present in the epithelium. Neuronal cells (olfactory cells and globose basal cells) were totally absent. The ultrastructure of the supporting cells, horizontal basal cells, and Bowman's glands was essentially similar to that in the normal olfactory epithelium. In the early postnatal period (P1-P7), cell types in the epithelium were the same as those in the normal olfactory epithelium. From P10 to P21, olfactory cells and globose basal cells had disappeared from the olfactory epithelium. At this period, the number of TUNEL-positive cells was significantly higher than that in the surrounding olfactory epithelium; ultrastructurally, many apoptotic figures were observed. This suggests that the epithelium consisting of supporting cells and horizontal basal cells is generated by the apoptotic death of olfactory cells and globose basal cells during postnatal development.

Odorants Modulate CREB in Olfactory Neurons

Stimulation of odorant receptors in olfactory neurons can result in an immediate and a delayed increase in intracellular cAMP. While the immediate cAMP response includes an influx of sodium and calcium and the generation of an action potential, the later cAMP signal is thought to produce long-term changes in neuron function, possibly through modulation of gene expression. Moon et al. report that phosphorylation of a transcription factor called the cAMP-responsive binding protein (CREB) occurred in the olfactory epithelium of mice when they were exposed to various odorants. Phosphorylation occurred at a specific serine residue, a modification required for CREB activation and DNA binding. Exposure of olfactory receptor cells to cGMP also stimulated phosphorylation of CREB. The authors previously proposed that the cGMP activates protein kinase G, which in turn activates adenyl cyclase and causes the observed delayed increase in intracellular cAMP. This report may extend this cGMP-cAMP signaling pathway to CREB and the transcription of specific genes. Moon, C., Sung, Y.-K., Reddy, R., and Ronnett, G.V. (1999) Odorants induce the phosphorylation of the cAMP response element binding protein in olfactory receptor neurons. Proc. Natl. Acad. Sci. U.S.A. 96 : 14605-14610. [Abstract] [Full Text]

Immunohistochemical Localization of Proliferating Cells and Epidermal Growth Factor Receptors in Mouse Olfactory Epithelium

We investigated age-related changes in proliferating cells and epidermal growth factor receptors (EGFRs) in mouse olfactory epithelium using an immunohistochemical method with the antiproliferating cell nuclear antigen (PCNA) antibody and the antihuman EGFRs antibody. Many PCNA-positive cells occurred in the surface and basal layers of the olfactory epithelium in the embryonal and neonatal mice. However, only some PCNA-positive cells occurred in the basal layer of adult mice, and only a few presented in the basal layer of aged mice. EGFRs were observed in all layers of the olfactory epithelium at the embryonal and neonatal stages, but were not identified in the olfactory epithelium at the adult or aged stages. We believe that a decrease in EGFRs in the olfactory epithelium induces the inhibition of cell proliferation, with the resultant atrophy of the olfactory epithelium.

Apoptosis in the development of the mouse olfactory epithelium

Apoptotic cells were detected in the mouse olfactory epithelium (OE) at different embryonic and postnatal stages by in situ nick translation (ISNT) and Tdt-mediated dUTP nick end-labeling (TUNEL) techniques. During development, the apoptotic process presented two peaks. One at E12 during the invagination of the olfactory placode and the second at E16 corresponding to olfactory axon synaptogenesis. Then, from E18, a sharp decrease in the number of apoptotic cells was observed and at E19 the apoptotic index reached low values that were maintained in postnatal stages, P1 and P8, and in the adult. Apoptotic nuclei belonged to mature as well as immature olfactory receptor neurons (ORNs). Indeed, double-labeling experiments evidenced apoptotic neurons immunopositive for olfactory marker protein (OMP), carnosine and GAP-43. According to our data, two apoptotic phases occur during early development. One is involved in the morphogenesis of the OE when this last is not yet, or poorly, connected to its target, the olfactory bulb (OB). The second peak of apoptosis is more closely dependent on the interplay between OE and OB.

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.

Factors regulating neurogenesis and programmed cell death in mouse olfactory epithelium.

To identify factors regulating neurogenesis and programmed cell death in mouse olfactory epithelium (OE), and to determine the mechanisms by which these factors act, we have studied mouse OE using two major experimental paradigms: tissue culture of embryonic OE and cell types isolated from it; and ablation of the olfactory bulb ('bulbectomy') of adult mice, a procedure that induces programmed cell death of olfactory receptor neurons (ORNS) and a subsequent surge of neurogenesis in the OE in vivo. Such experiments have been used to characterize the cellular stages in the ORN lineage, leading to the realization that there are at least two distinct stages of proliferating neuronal progenitor cells interposed between the ORN and the stem cell that ultimately gives rise to it. The identification of a number of different factors that act to regulate proliferation and survival of ORNs and progenitor cells suggests that these multiple cell stages may each serve as a control point at which neuron number in the OE is regulated. Our recent studies of neuronal colony-forming progenitors (putative stem cells) of the OE suggest that even these cells, at the earliest stage in the ORN lineage so far identified, are subject to such regulation: if colony-forming progenitors are cultured in the presence of a large excess of differentiated ORNs, then the production of new neurons by progenitors is dramatically inhibited. This result suggests that differentiated ORNs produce a signal that feeds back to inhibit neurogenesis by their own progenitors, and provides a possible explanation for the observation that ORN death, consequent to bulbectomy, results in increased neurogenesis in the OE in vivo: death of ORNs may release neuronal progenitor cells from this inhibitory signal, produced by the differentiated ORNs that lie near them in the OE. Our current experiments are directed toward identifying the molecular basis of this inhibitory signal, and the cellular mechanism(s) by which it acts.

Cell death, phagocytosis, and neurogenesis in mouse olfactory epithelium and vomeronasal organ after colchicine treatment.

The cytotoxic agent colchicine induced apoptotic cell death in the mouse olfactory epithelium and vomeronasal organ. The terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) method revealed the presence of many apoptotic bodies in the middle to basal region of the septal olfactory epithelium and vomeronasal organ near the boundary of the respiratory epithelium at 1 day after intraperitoneal (i.p.) injection of colchicine (4 mg/kg). In some areas of the nasal turbinates, massive apoptosis was observed in the olfactory epithelium. Electron micrographs showed that immature olfactory cells and globose basal cells were killed by the colchicine and had been phagocytized by the supporting cells and macrophages. In some areas of the nasal turbinates, mature olfactory cells were also killed, and thus only the supporting cells and horizontal basal cells remained in the epithelium. Bromodeoxyuridine (BrdU) labeling showed that regeneration occurred in the septum and vomeronasal organ at 4-6 days after colchicine treatment; however, there were no regenerated olfactory cells in some areas of the turbinates up to 30 days after colchicine treatment.

Distribution of neuronal intermediate filament proteins in the developing mouse olfactory system.

The distribution of neuronal intermediate filament proteins in the developing mouse olfactory bulb and olfactory epithelium was characterized by immunocytochemical approach. Antibodies against alpha-internexin, neurofilament triplet proteins (NFTPs; NF-L, NF-M, and NF-H) and peripherin were used to determine their expression at different developmental stages. Alpha-internexin and peripherin were first found to be co-localized in the olfactory neuroepithelium during early development. At the perinatal stage, expression patterns of alpha-internexin and peripherin are distinguishable by spatial and temporal manner: peripherin is predominantly expressed in the olfactory nerves; whereas alpha-internexin is expressed in both olfactory nerves and olfactory bulb. Our observation suggests that peripherin as well as alpha-internexin may play some roles in the process formation of olfactory nerves during development. In the developing olfactory periglomerulus, alpha-internexin was found around postnatal Day 3, whereas NFTPs were not observed until postnatal Day 7. Our data showed that the expression of alpha-internexin preceded those of the NFTPs in most neurons of the developing olfactory bulb. Some small neurons in the adult olfactory bulb were uniquely labeled with antibody to alpha-internexin. Our results suggest that alpha-internexin may play a functional role in the neuronal cytoarchitecture of developing olfactory system, and can be a neuronal marker for detecting postmitotic migrating neurons in the adult olfactory bulb.

Upregulation of neural growth-associated protein and neural cell adhesion molecule in mouse olfactory epithelium and axons after unilateral removal of the olfactory bulb.

The expression of synaptosomal-associated protein (SNAP-25), neural growth-associated protein (GAP-43) and neural cell adhesion molecule (NCAM) were studied in mouse olfactory cells and axons for 2 weeks following unilateral bulbectomy. The olfactory cells and axons in the control olfactory epithelium were positive for SNAP-25 but levels decreased in the atrophic olfactory epithelium 3 days after bulbectomy. There was no expression of SNAP-25 in the olfactory epithelium on the bulbectomy side 7 days after bulbectomy, indicating that this protein may be a good marker for the degeneration of olfactory cells. The expression of NCAM was still found in the atrophic olfactory epithelium at 7 days after bulbectomy, while the expression of NCAM in the olfactory epithelium of the bulbectomy side was stronger than that on the control side at 14 days after bulbectomy. The expression of GAP-43 in the olfactory axonal bundles of the bulbectomy side at 3 and 4 days after bulbectomy was stronger than that on the control side. These results suggest that upregulation of NCAM may be related to the regeneration of the olfactory cells, with upregulation of GAP-43 probably playing a role in axonal regeneration after bulbectomy.

Colchicine-induced cell death and proliferation in the olfactory epithelium and vomeronasal organ of the mouse.

The cytotoxic agent colchicine induced apoptotic cell death and subsequent regeneration in the mouse olfactory epithelium and vomeronasal organ. The TUNEL method revealed the presence of many apoptotic bodies in the middle to basal region of the septal olfactory epithelium and vomeronasal organ near the boundary of the respiratory epithelium at 1 day after a single i.p. injection of colchicine (4 mg/kg b.w.). In some regions of the third and the fourth nasal turbinates, massive apoptosis was observed in the olfactory epithelium. Electron micrographs of the septum showed that immature olfactory cells and globose basal cells were killed by the colchicine and had been phagocytized by the supporting cells and macrophages. In the vomeronasal organ, immature sensory cells and precursors died in response to the colchicine. In response to cell death, active proliferation of precursor cells (globose basal cells) and subsequent regeneration of olfactory cells occurred in the olfactory epithelium and vomeronasal organ. Incorporation of the mitotic tracer BrdU by precursor cells reached its peak at 4 days after colchicine treatment in the vomeronasal organ, and at 6 to 7 days in the olfactory epithelium; however, in some regions in the third and the fourth nasal turbinates, where many olfactory cells and globose basal cells had died by colchicine effect, the regeneration did not occur even in 1 month, forming the epithelium of only supporting cells and horizontal basal cells. In the next month, these regions became normal olfactory epithelium. This suggests that the globose basal cells in the surrounding normal olfactory epithelium might invade these regions to give rise to the olfactory cells.

Primary Culture of Adult Mouse Olfactory Receptor Neurons

Olfactory receptor neurons (ORNs) are unique because they can be replaced by stem cells throughout life. Previous studies have demonstrated that adult mouse olfactory epithelium (OE) injured by exposure to ZnSO4through nasal irrigation can stimulate stem cell mitotic activityin situ, which continues when placed in culture. We report on an improved ZnSO4delivery method, mist inhalation, which produces more consistent and greater yields of OE cells. Cultures established following this method contained bipolar, nest, fusiform, and giant cells. The bipolar cells usually underwent asymmetric process development. Some bipolar cells reacted positively to neuron-specific antibodies and were immunonegative for keratin and glia-specific proteins, suggesting that they were ORNs. Those that were negative for the neuron-specific proteins may represent either neuron progenitors or olfactory ensheathing cells. The fusiform cells were relatively small and undifferentiated, exposure to brain-derived neurotrophic factor resulted in their decrease and an increase in bipolar cells. Therefore, they might be the stem cells. The nest cells had morphological characteristics of epithelia and bound keratin antibodies. The giant cells had the morphology of epithelial cells but were negative for keratin; they may represent a unique cell population induced by the ZnSO4. These results indicate that the major cell types of intact OE are present in our cultures, and each retains characteristics foundin situ. The mist inhalation method provides anin vitropopulation of adult mitotically active neurons for study.

Retinoid signaling distinguishes a subpopulation of olfactory receptor neurons in the developing and adult mouse

We asked whether retinoic acid (RA) influences olfactory receptor neurons (ORNs) in the developing and mature mouse olfactory epithelium (oe). The distribution of retinoid receptors and binding proteins in the oe changes between embryonic days 11.5 and 13.5, the period when ORNs first differentiate and send axons into the nascent olfactory nerve. Coincident with this change, RA, which is produced in the frontonasal mesenchyme at these ages, begins to activate gene expression in a bilaterally symmetric subset of ORNs in the dorsolateral oe, as judged by the expression of an RA-responsive transgene. Axons from these RA-activated ORNs are segregated in the olfactory nerve as it extends through the frontonasal mesenchyme toward the forebrain. In vitro, RA potentiates ORN neurite growth on laminin, which, in the embryo, is found in a stripe of frontonasal mesenchyme directly associated with the olfactory nerve. RA does not modify growth on fibronectin, type IV collagen, or L1, which olfactory axons encounter in different regions of the territory between the olfactory epithelium and the brain. The pattern of RA-mediated transcriptional activation and axon segregation persists in early postnatal mice, and RA signaling can be recognized in a subset of adult ORNs in the dorsolateral oe. Thus, RA-mediated gene expression distinguishes a subpopulation of ORNs in a distinct region of the oe during the early development of the olfactory pathway, and may influence differentiation and axonal projections of ORNs in this region throughout life. J. Comp. Neurol. 394:445–461, 1998. © 1998 Wiley-Liss, Inc.

Retinoid signaling distinguishes a subpopulation of olfactory receptor neurons in the developing and adult mouse

We asked whether retinoic acid (RA) influences olfactory receptor neurons (ORNs) in the developing and mature mouse olfactory epithelium (oe). The distribution of retinoid receptors and binding proteins in the oe changes between embryonic days 11.5 and 13.5, the period when ORNs first differentiate and send axons into the nascent olfactory nerve. Coincident with this change, RA, which is produced in the frontonasal mesenchyme at these ages, begins to activate gene expression in a bilaterally symmetric subset of ORNs in the dorsolateral oe, as judged by the expression of an RA-responsive transgene. Axons from these RA-activated ORNs are segregated in the olfactory nerve as it extends through the frontonasal mesenchyme toward the forebrain. In vitro, RA potentiates ORN neurite growth on laminin, which, in the embryo, is found in a stripe of frontonasal mesenchyme directly associated with the olfactory nerve. RA does not modify growth on fibronectin, type IV collagen, or L1, which olfactory axons encounter in different regions of the territory between the olfactory epithelium and the brain. The pattern of RA-mediated transcriptional activation and axon segregation persists in early postnatal mice, and RA signaling can be recognized in a subset of adult ORNs in the dorsolateral oe. Thus, RA-mediated gene expression distinguishes a subpopulation of ORNs in a distinct region of the oe during the early development of the olfactory pathway, and may influence differentiation and axonal projections of ORNs in this region throughout life.

きゅう上皮第５型細胞に関する研究

The olfactory epithelium has been shown to contain fifth-type cells and microvillar cells and olfactory receptor cells along with supporting and basal cells. However, the morphological differences among them are unknown, especially between the former two, and most of their functions are still unclear. In this study, the fifth-type cell and the microvillar cell in the olfactory epithelium of mouse were micromorphologically investigated by SEM and TEM. With the aim of elucidation their functions, the morphological change in these cells after resection of olfactory bulb were studied. In addition, the changes in the olfactory epihelium after HRP injections into the postganglionic fiber for the trigeminal nerve and the olfactory bulb were examined. The TEM observation revealed that the fifth-type cell has finger-like microvilli, which are strong and straight. The microvilli were characterized by a specific core structure consisting of microfilament bundles. On the other band, the microvilli of the microvillar cell were meandering and had no core structure, indicating that the two cells are clearly different types. By SEM observation, neither the fifth-type cell nor the microvillar cell was found in the normal olfactory epithelium. When the olfactory cillial mat disappeared as a result of recection of the olfactory bulb, the fifth-type cell became observable. On the 300th-day after the resection, it was found that the olfactory receptor cells had disappeared and the microvilli of the supporting cells were shortened. Thus, the surface structure of the microvillar cell became clearly observable. Then, the microvilli were found to be shorter than those of the fifth-type cell and were distributed radially. Neither the fifth-type cell nor the microvillar cell was not affected by resection of the olfactory bulb. Most of the olfactory vesicles were HRP positive after the HRP injection into the olfactory bulb; however, HRP was not detected in either the fifth-type cells or the microvillar cells. After the HRP injection into the trigeminal postganglionic fiber, it was detectable in part of the nerves in the lamina propria mucosa and the epithelal basement, but not in the fifth-type cell or microvillar cell. These results suggest that the fifth-type cell is a mechanoreceptor for a system other than the olfactory one and the microvillar cell is a kind of supporting cell in an early stage or final stage near death.

TrkA Expression in Mouse Olfactory Tract following Axotomy of Olfactory Nerves

The olfactory bulb is one of the brain regions that synthesizes the nerve growth factor (NGF). Functional roles of the bulbar NGF remain to be determined. The aim of the present study was, using an antibody specific to the high-affinity NGF receptor (trkA), to examine immunohistochemically the distribution of the NGF receptor in the mouse olfactory tract, under normal conditions and during regenerative processes. In normal mouse olfactory epithelia, trkA immunoreactive cell bodies were only seen in basal cells. Cell bodies of olfactory receptor cells did not express trkA immunoreactivity, but their neuronal processes (olfactory nerve fibres and bundles in the olfactory mucosa and the olfactory bulb) displayed trkA immunoreactivity. After axotomy of olfactory nerves, regenerating olfactory cells (basal cells and olfactory receptor cells) expressed trkA immunoreactivity in intramucosal and intrabulbar neuronal processes of olfactory receptor cells. These results suggest involvement of the bulbar NGF in the process of synaptogenesis and/or regeneration of the olfactory nervous system.

Coordinate reduction in cell proliferation and cell death in mouse olfactory epithelium from birth to maturity

We investigated cell proliferation and cell death in the olfactory epithelium (OE) of mice from birth to maturity using bromodeoxyuridine and terminal deoxynucleotidyl transferase nick and labeling. We show that cell death events and proliferative activity diminish concomitantly with age in the OE. Thus, the age-dependent and coordinate diminution in cell proliferative activity and cell death events may serve to maintain the thickness of the OE as mice mature and age.