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Olfactory Sensory Neurons (olfactory + sensory_neuron)
Selected AbstractsOlfactory sensory axon growth and branching is influenced by sonic hedgehogDEVELOPMENTAL DYNAMICS, Issue 7 2009Qizhi Gong Abstract Olfactory sensory neuron (OSN) axons extend from the olfactory epithelium to the olfactory bulb without branching until they reach their target region, the glomerulus. In this report, we present evidence to support the involvement of sonic hedgehog in promoting rat olfactory sensory axons to branch and to enter into the glomerulus. Sonic hedgehog (Shh) protein is detected in the glomeruli of the olfactory bulb, whereas its transcript is expressed in the mitral and tufted cells, suggesting that Shh in the glomeruli is produced by mitral and tufted cells. In primary OSN cultures, Shh-N peptide promotes olfactory axon branching. When Shh function is neutralized in vivo by its antibody, growth of newly generated OSN axons into the glomeruli is vastly reduced. Developmental Dynamics 238:1768,1776, 2009. © 2009 Wiley-Liss, Inc. [source] Plasma membrane Ca2+ -ATPase in the cilia of olfactory receptor neurons: possible role in Ca2+ clearanceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007Karen Castillo Abstract Olfactory sensory neurons respond to odorants increasing Ca2+ concentrations in their chemosensory cilia. Calcium enters the cilia through cAMP-gated channels, activating Ca2+ -dependent chloride or potassium channels. Calcium also has a fundamental role in odour adaptation, regulating cAMP turnover rate and the affinity of the cyclic nucleotide-gated channels for cAMP. It has been shown that a Na+/Ca2+ exchanger (NCX) extrudes Ca2+ from the cilia. Here we confirm previous evidence that olfactory cilia also express plasma membrane Ca2+ -ATPase (PMCA), and show the first evidence supporting a role in Ca2+ removal. Both transporters were detected by immunoblot of purified olfactory cilia membranes. The pump was also revealed by immunocytochemistry and immunohistochemistry. Inside-out cilia membrane vesicles transported Ca2+ in an ATP-dependent fashion. PMCA activity was potentiated by luminal Ca2+ (K0.5 = 670 nm) and enhanced by calmodulin (CaM; K0.5 = 31 nm). Both carboxyeosin (CE) and calmidazolium reduced Ca2+ transport, as expected for a CaM-modulated PMCA. The relaxation time constant (,) of the Ca2+ -dependent Cl, current (272 ± 78 ms), indicative of luminal Ca2+ decline, was increased by CE (2181 ± 437 ms), by omitting ATP (666 ± 49 ms) and by raising pH (725 ± 65 ms), suggesting a role of the pump on Ca2+ clearance. Replacement of external Na+ by Li+ had a similar effect (, = 442 ± 8 ms), confirming the NCX involvement in Ca2+ extrusion. The evidence suggests that both Ca2+ transporters contribute to re-establish resting Ca2+ levels in the cilia following olfactory responses. [source] Subzonal organization of olfactory sensory neurons projecting to distinct glomeruli within the mouse olfactory bulbTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2003Olga Levai Abstract Olfactory sensory neurons located in the nasal neuroepithelium send their axons directly into the olfactory bulb, where they contact the dendrites of second-order neurons in specialized spherical structures called glomeruli; each sensory neuron projects to a single glomerulus. All neurons expressing the same odorant receptor gene are confined to distinct zones within the epithelium and converge their axons onto a small number of common glomeruli. In the present study, we analyzed transgenic mouse lines in which the projection of a neuron population expressing a particular receptor gene can be visualized as a result of axonal markers that are coexpressed. The target glomeruli could thus reproducibly be identified and allowed to deposit retrograde tracers precisely. After an appropriate incubation time, olfactory sensory neurons within distinct areas of the olfactory epithelium were labeled. The two subpopulations of neurons retrogradely stained by differently colored fluorescent dyes deposited at the dorsal and the dorsomedial glomerulus, respectively, were found to be segregated within distinct areas of the expression zone, where the cells expressing the same receptor type displayed a stochastic distribution. J. Comp. Neurol. 458:209,220, 2003. © 2003 Wiley-Liss, Inc. [source] Olfactory ensheathing cell membrane properties are shaped by connectivityGLIA, Issue 6 2010Lorena Rela Abstract Olfactory ensheathing cells (OECs) have been repeatedly implicated in mediating plasticity, particularly in situ in the olfactory nerve in which they support the extension of olfactory sensory neuron (OSN) axons from the olfactory epithelium to the olfactory bulb (OB). OECs are specialized glia whose processes surround OSN axon fascicles within the olfactory nerve and across the OB surface. Despite their purported importance in promoting axon extension, and following transplants, little is known about either morphology or biophysical properties of OECs in situ. In particular, cell,cell interactions that may influence OEC function are largely unexplored. Here, we studied OEC connectivity and morphology in slice preparations, preserving tissue structure and cell,cell interactions. Our analyses showed that OECs form a matrix of cellular projections surrounding axons, unique among glia, and express high levels of connexin-43. Lucifer Yellow injections revealed selective dye coupling among small subgroups of OECs. Two types of OECs were biophysically distinguished with whole-cell voltage-clamp recordings: (1) with low-input resistance (Ri), linear current profiles, and frequently dye coupled; and (2) with high Ri, nonlinear current profiles, and infrequent dye coupling. Pharmacological blockade of gap junctions changed OEC membrane properties such that linear OECs became nonlinear. Double recordings indicated that the appearance of the nonlinear current profile was associated with the loss of electrical coupling between OECs. We conclude that the diversity of OEC current profiles can be explained by differences in gap-junction connectivity and discuss implications of this diversity for OEC influences on axon growth and excitability. © 2009 Wiley-Liss, Inc. [source] Wnt/frizzled family members mediate olfactory sensory neuron axon extensionTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2008Diego J. Rodriguez-Gil Abstract A comprehensive model has yet to emerge, but it seems likely that numerous mechanisms contribute to the specificity of olfactory sensory neuron (OSN) axon innervation of the olfactory bulb. Elsewhere in the nervous system the Wnt/Fz family has been implicated in patterning of anterior-posterior axes, cell type specification, cell proliferation, and axon guidance. Because of our work describing cadherin-catenin family member expression in the primary olfactory pathway, and because mechanisms of Wnt-Fz interactions can depend in part on catenins, we were encouraged to explore Wnt-Fz expression and function in OSN axon extension. Here, we show that OSNs express Fz-1, Fz-3, and Wnt-5a, whereas olfactory ensheathing cells (OECs) express Wnt-4. Fz-7 is also expressed in the olfactory nerve by cells that delineate large axon fascicles, but are negative for OEC markers. Fz-1 showed a developmental downregulation. However, in adults it is expressed at different levels across the olfactory epithelium and in restricted glomeruli across the olfactory bulb, suggesting an important role in the formation and maintenance of OSN connections to the olfactory bulb. Reporter TOPGAL mice demonstrated that some OECs located in the inner olfactory nerve layer can respond to Wnt ligands. Of further interest, we show here with in vitro assays that Wnt-5a increases OSN axon outgrowth and alters growth cone morphology. Our data point to a key role for Wnt/Fz molecules in the development of the mouse olfactory system, providing complementary mechanisms required for OSN axon extension and coalescence. J. Comp. Neurol. 511:301,317, 2008. © 2008 Wiley-Liss, Inc. [source] The proto-oncogene BCL6 promotes survival of olfactory sensory neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2010Joji M. Otaki Abstract For the mammalian olfactory epithelium to continually detect odorant, neuronal survival, apoptosis, and regeneration must be coordinated. Here, we showed that the proto-oncogene BCL6, which encodes a transcriptional repressor required for lymphocyte terminal differentiation, contributes to the survival of olfactory sensory neurons (OSNs). In the olfactory epithelia of the BCL6 null mutant mice, many OSNs were positive for both OMP and GAP43. The epithelium was relatively thinner, showing many apoptotic signals. These characters were phenotypically similar to those of the wild-type mice treated with nasal lectin irrigation, which acutely induces apoptosis of OSNs. Odorant receptors were expressed normally in the epithelia of the mutant mice, and their overall expression profile based on DNA microarray analyses was roughly similar to that of the apoptosis-induced olfactory epithelia of the wild-type mice. Experimental increase of BCL6 together with green fluorescent protein in OSNs using adenovirus-mediated gene transfer made the epifluorescence last longer than the control fluorescence without exogenous BCL6 after the nasal lectin irrigation, indicating that BCL6 made the infected neurons survive longer. We conclude that BCL6 plays an active role in the survival of OSNs as an anti-apoptotic factor and confers immature OSNs enough time to fully differentiate into mature ones. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 424-435, 2010 [source] The molecular receptive range of an olfactory receptor in vivo (Drosophila melanogaster Or22a)DEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006Daniela Pelz Abstract Understanding how odors are coded within an olfactory system requires knowledge about its input. This is constituted by the molecular receptive ranges (MRR) of olfactory sensory neurons that converge in the glomeruli of the olfactory bulb (vertebrates) or the antennal lobe (AL, insects). Aiming at a comprehensive characterization of MRRs in Drosophila melanogaster we measured odor-evoked calcium responses in olfactory sensory neurons that express the olfactory receptor Or22a. We used an automated stimulus application system to screen [Ca2+] responses to 104 odors both in the antenna (sensory transduction) and in the AL (neuronal transmission). At 10,2 (vol/vol) dilution, 39 odors elicited at least a half-maximal response. For these odorants we established dose-response relationships over their entire dynamic range. We tested 15 additional chemicals that are structurally related to the most efficient odors. Ethyl hexanoate and methyl hexanoate were the best stimuli, eliciting consistent responses at dilutions as low as 10,9. Two substances led to calcium decrease, suggesting that Or22a might be constitutively active, and that these substances might act as inverse agonists, reminiscent of G-protein coupled receptors. There was no difference between the antennal and the AL MRR. Furthermore we show that Or22a has a broad yet selective MRR, and must be functionally described both as a specialist and a generalist. Both these descriptions are ecologically relevant. Given that adult Drosophila use approximately 43 ORs, a complete description of all MRRs appears now in reach. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Secreted TARSH regulates olfactory mitral cell dendritic complexityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Ting-Wen Cheng Abstract Olfactory sensory neurons synapse with mitral cells to form stereotyped connections in the olfactory bulb (OB). Mitral cell apical dendrites receive input from olfactory sensory neurons expressing the same odorant receptor. During development, this restricted dendritic targeting of mitral cells is achieved through eliminating elaborated dendritic trees to a single apical dendrite. Through a genome-wide microarray screen, we identified TARSH (Target of NESH SH3) as a transiently expressed molecule in mitral cells during the dendritic refinement period. TARSH expression is restricted to pyramidal neurons along the main olfactory pathway, including the anterior olfactory nucleus and piriform cortex. The dynamic TARSH expression is not altered when odor-evoked activity is blocked by naris closure or in AC3 knockout mice. We also demonstrate that TARSH is a secreted protein. In dissociated OB cultures, secreted TARSH promotes the reduction of mitral cell dendritic complexity and restricts dendritic branching and outgrowth of interneurons. Dendritic morphological changes were also observed in mitral cells overexpressing TARSH themselves. We propose that TARSH is part of the genetic program that regulates mitral cell dendritic refinement. [source] Single olfactory sensory neurons simultaneously integrate the components of an odour mixtureEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003Patricia Duchamp-Viret Abstract Most odours are complex mixtures. However, the capacities of olfactory sensory neurons (OSNs) to process complex odour stimuli have never been explored in air-breathing vertebrates. To face this issue, the present study compares the electrical responses of single OSNs to two odour molecules, delivered singly and mixed together, in rats in vivo. This work is the first aimed at demonstrating that single OSNs simultaneously integrate several chemical signals and which, furthermore, attempts to describe such processes for the whole concentration range over which single OSNs can work. The results stress that complex interactions occur between components in odour mixtures and that OSN responses to such mixtures are not simply predictable from the responses to their components. Three types of interactions are described. They are termed suppression, hypoadditivity and synergy, in accord with psychophysical terminology. This allows us to draw links between peripheral odour reception and central odour coding. Indeed, events occurring in single OSNs may account for the dominating or even the masking effects of odour molecules in complex mixtures, i.e. for the prevailing action of a minor component in the final qualitative perception of a mixture. We conclude that our observations with binary mixtures anticipate the complexity of processes which may rise at the level of a single OSN in physiological conditions. Following this hypothesis, a natural odour would induce a multi-chemical integration at the level of single OSNs which may result in refining their individual odour-coding properties, leading them to play a crucial role in the final performance of the olfactory system. [source] Developmental elimination of ectopic projection sites for the transgenic OR gene that has lost zone specificity in the olfactory epitheliumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2003Hiroko Nakatani Abstract In rodents, olfactory receptor (OR) genes are expressed in one of four zones in the olfactory epithelium (OE), and olfactory sensory neurons (OSNs) expressing the same OR project their axons to a specific set of glomeruli on the olfactory bulb (OB). Using the yeast artificial chromosome (YAC) transgenic system, we have analysed the expression of the murine OR gene MOR29A of the MOR28 cluster located on chromosome 14. Although expression of the endogenous MOR29A was restricted to the most dorsomedial zone, the transgenic MOR29A (Tg MOR29A) was expressed in all four zones of the OE. When the OB of the transgenic mouse was analysed, the axons of the OSNs expressing Tg MOR29A were found to project not only to the dorsal side but also to the ventral side of the OB as well. The ectopic projection sites on the ventral side gradually disappear during postnatal development. Naris occlusion prevents this elimination, suggesting that odorant stimulation is involved in eliminating the ectopic projection sites. [source] A novel brain receptor is expressed in a distinct population of olfactory sensory neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000Sidonie Conzelmann Abstract Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor-expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules. [source] Amino acids involved in conformational dynamics and G protein coupling of an odorant receptor: targeting gain-of-function mutationJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Aya Kato Abstract Thousands of different odorants are recognized and discriminated by odorant receptors (ORs) in the guanine nucleotide-binding protein (G protein)-coupled seven-transmembrane receptor family. Odorant-bound ORs stimulate Gs-type G proteins, G,olf, which in turn activates cAMP-mediated signaling pathway in olfactory sensory neurons. To better understand the molecular basis for OR activation and G protein coupling, we analyzed the effects of a series of site-directed mutations of mouse ORs, on function. Mutations of conserved amino acid residues in an intracellular loop or the C-terminus resulted in loss of activity without impairing ligand-binding activity, indicating that these residues are involved in G,s/olf coupling. Moreover, mutation of the serine in KAFSTC, the OR-specific sequence motif, resulted in a dramatic increase in odorant responsiveness, suggesting that the motif is involved in a conformational change of the receptor that regulates G protein coupling efficiency. Our results provide insights into how ORs switch from an inactive to an active state, as well as where and how activated ORs interact with G proteins. [source] Regulation of intracellular cyclic GMP levels in olfactory sensory neuronsJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Cheil Moon Abstract Cyclic AMP is the primary second messenger mediating odorant signal transduction in mammals. A number of studies indicate that cyclic GMP is also involved in a variety of other olfactory signal transduction processes, including adaptation, neuronal development, and long-term cellular responses in the setting of odorant stimulation. However, the mechanisms that control the production and degradation of cGMP in olfactory sensory neurons (OSNs) remain unclear. Here, we investigate these mechanisms using primary cultures of OSNs. We demonstrate that odorants increase cGMP levels in intact OSNs in vitro. Different from the rapid and transient cAMP responses to odorants, the cGMP elevation is both delayed and sustained. Inhibition of soluble guanylyl cyclase and heme oxygenase blocks these odorant-induced cGMP increases, whereas inhibition of cGMP PDEs (phosphodiesterases) increases this response. cGMP PDE activity is increased by odorant stimulation, and is sensitive to both ambient calcium and cAMP concentrations. Calcium stimulates cGMP PDE activity, whereas cAMP and protein kinase A appears to inhibit it. These data demonstrate a mechanism by which odorant stimulation may regulate cGMP levels through the modulation of cAMP and calcium level in OSNs. Such interactions between odorants and second messenger systems may be important to the integration of immediate and long-term responses in the setting odorant stimulation. [source] Odor discrimination by G protein-coupled olfactory receptorsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2002Kazushige Touhara Abstract The vertebrate olfactory system possesses a remarkable capacity to recognize and discriminate a variety of odorants by sending the coding information from peripheral olfactory sensory neurons in the olfactory epithelium to the olfactory bulb of the brain. The recognition of odorants appear to be mediated by a G protein-coupled receptor superfamily that consists of ,1% of total genes in vertebrates. Since the first discovery of the olfactory receptor gene superfamily in the rat, similar chemosensory receptors have been found in various species across different phyla. The functions of these receptors, however, had been uncharacterized until the recently successful functional expression and ligand screening of some olfactory receptors in various cell expression systems. The functional cloning of odorant receptors from single olfactory neurons allowed for the identification of multiple receptors that recognized a particular odorant of interest. Reconstitution of the odorant responses demonstrated that odorant receptors recognized various structurally-related odorant molecules with a specific molecular receptive range, and that odor discrimination is established based on a combinatorial receptor code model in which the identities of different odorants are encoded by a combination of odorant receptors. The receptor code for an odorant changes at different odorant concentrations, consistent with our experience that perceived quality of an odorant changes at different concentrations. The molecular bases of odor discrimination at the level of olfactory receptors appear to correlate well with the receptive field in the olfactory bulb where the input signal is further processed to create the specific odor maps. Microsc. Res. Tech. 58:135,141, 2002. © 2002 Wiley-Liss, Inc. [source] Chemical stress induces the unfolded protein response in olfactory sensory neuronsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 10 2010Neeraja Sammeta Abstract More than any other neuron, olfactory sensory neurons are exposed to environmental insults. Surprisingly, their only documented response to damaging stress is apoptosis and subsequent replacement by new neurons. However, they expressed unfolded protein response genes, a transcriptionally regulated defense mechanism activated by many types of insults. The unfolded protein response transcripts Xbp1, spliced Xbp1, Chop (Ddit3), and BiP (Hspa5) were decreased when external access of stressors was reduced by blocking a nostril (naris occlusion). These transcripts and Nrf2 (Nfe2l2) were increased by systemic application of tunicamycin or the selective olfactotoxic chemical methimazole. Methimazole's effects overcame naris occlusion, and the unfolded protein response was independent of odor-evoked neuronal activity. Chemical stress is therefore a major and chronic activator of the unfolded protein response in olfactory sensory neurons. Stress-dependent repression of the antiapoptotic gene Bcl2 was absent, however, suggesting a mechanism for disconnecting the UPR from apoptosis and tolerating a chronic unfolded protein response. Environmental stressors also affect both the sustentacular cells that support the neurons and the respiratory epithelia, because naris occlusion decreased expression of the xenobiotic chemical transformation enzyme Cyp2a5 in sustentacular cells, and both naris occlusion and methimazole altered the abundance of the antibacterial lectin Reg3g in respiratory epithelia. J. Comp. Neurol. 518:1825,1836, 2010. © 2009 Wiley-Liss, Inc. [source] Wnt/frizzled family members mediate olfactory sensory neuron axon extensionTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2008Diego J. Rodriguez-Gil The main olfactory epithelium from a postnatal day 4 mouse. Tissue was stained for olfactory marker protein (OMP, red), Wnt-5a (green) and DRAQ5 (blue). All the mature, OMP-expressing, olfactory sensory neurons showed Wnt-5a expression. Wnt-5a expression appears to cap the nucleus of olfactory sensory neurons apically in a position that is consistent with the localization of the endoplasmic reticulum and Golgi apparatus. J. Comp. Neurol. 511:301,317, 2008. © 2008 Wiley-Liss, Inc. [source] Wnt/frizzled family members mediate olfactory sensory neuron axon extensionTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2008Diego J. Rodriguez-Gil The main olfactory epithelium from a postnatal day 4 mouse. Tissue was stained for olfactory marker protein (OMP, red), Wnt-5a (green) and DRAQ5 (blue). All the mature, OMP-expressing, olfactory sensory neurons showed Wnt-5a expression. Wnt-5a expression appears to cap the nucleus of olfactory sensory neurons apically in a position that is consistent with the localization of the endoplasmic reticulum and Golgi apparatus. J. Comp. Neurol. 511:307,317, 2008. © 2008 Wiley-Liss, Inc. [source] Subzonal organization of olfactory sensory neurons projecting to distinct glomeruli within the mouse olfactory bulbTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2003Olga Levai Abstract Olfactory sensory neurons located in the nasal neuroepithelium send their axons directly into the olfactory bulb, where they contact the dendrites of second-order neurons in specialized spherical structures called glomeruli; each sensory neuron projects to a single glomerulus. All neurons expressing the same odorant receptor gene are confined to distinct zones within the epithelium and converge their axons onto a small number of common glomeruli. In the present study, we analyzed transgenic mouse lines in which the projection of a neuron population expressing a particular receptor gene can be visualized as a result of axonal markers that are coexpressed. The target glomeruli could thus reproducibly be identified and allowed to deposit retrograde tracers precisely. After an appropriate incubation time, olfactory sensory neurons within distinct areas of the olfactory epithelium were labeled. The two subpopulations of neurons retrogradely stained by differently colored fluorescent dyes deposited at the dorsal and the dorsomedial glomerulus, respectively, were found to be segregated within distinct areas of the expression zone, where the cells expressing the same receptor type displayed a stochastic distribution. J. Comp. Neurol. 458:209,220, 2003. © 2003 Wiley-Liss, Inc. [source] Treatment of Olfactory Dysfunction, II: Studies With Minocycline,THE LARYNGOSCOPE, Issue 12 2004R C. Kern MD Abstract Objectives/Hypothesis: The treatment of anosmia has changed minimally since the early 1970s, despite dramatic advances in the understanding of the molecular biology of olfaction. Recent studies from the authors' laboratory have suggested that most common causes of clinical olfactory dysfunction, including rhinosinusitis, appear to be associated with increased apoptotic death of olfactory sensory neurons. This appears to result in a decline in the number of functioning mature olfactory sensory neurons, despite the capacity of the olfactory epithelium for regeneration. The current study evaluated the ability of the antibiotic minocycline to inhibit olfactory sensory neuron apoptosis. This drug is known to inhibit apoptosis separate from its anti-infective properties. Olfactory sensory neuron apoptosis was triggered by surgical deafferentation ("bulbectomy"), the standard experimental model. Earlier studies have indicated that bulbectomy and sinusitis invoke similar proteolytic enzyme cascades in olfactory sensory neurons. Study Design: Histological analysis of animal olfactory tissue. Methods: Mice underwent unilateral olfactory bulbectomy to induce apoptotic olfactory sensory neuron death, with and without 45 mg/kg intraperitoneal minocycline given 12 hours before surgery and every 12 hours until death. Mice were killed at 2 and 4 days after bulbectomy and assessed for activation of capsase-3 and olfactory sensory neuron survival by immunohistochemical analysis. Results: Minocycline resulted in partial suppression of cell death at 2 days after surgery when compared with untreated animals. Conclusion: Minocycline inhibits olfactory sensory neuron death in the face of a potent pro-apoptotic stimulus. This drug is well tolerated and is currently undergoing human trials for the management of a variety of neurological disorders associated with apoptosis. The current results suggest that minocycline may be efficacious in the management of peripheral olfactory loss as well. [source] Pathology of the Olfactory Epithelium: Smoking and Ethanol Exposure,THE LARYNGOSCOPE, Issue 8 2004J Vent MD Abstract Objective: To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis. Study Design: A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke. Methods: Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis. Results: Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage. Conclusions: These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium. [source] | |||||||||||||