Constitutive and evoked release of ATP in adult mouse olfactory epithelium.

In adult olfactory epithelium (OE), ATP plays a role in constant cell turnover and post-injury neuroregeneration. We previously demonstrated that constitutive and ATP-evoked ATP release are present in neonatal mouse OE and underlie continuous cell turn-over and post-injury neuroregeneration, and that activation of purinergic P2X receptors is involved in the evoked release. We hypothesized that both releases are present in adult mouse OE.

Cannabinoid receptor signaling induces proliferation but not neurogenesis in the mouse olfactory epithelium.

The olfactory epithelium actively generates neurons through adulthood, and this neurogenesis is tightly regulated by multiple factors that are not fully defined. Here, we examined the role of cannabinoids in the regulation of neurogenesis in the mouse olfactory epithelium. In vivo proliferation and cell lineage studies were performed in mice (C57BL/6 and cannabinoid type 1 and 2 receptor deficient strains) treated with cannabinoids directly (WIN 55,212-2 or 2-arachidonylglycerol ether) or indirectly via inhibition of cannabinoid hydrolytic enzymes.

An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction.

Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium have not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium.

Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation.

Losing the sense of smell because of aging compromises health and quality of life. In the mouse olfactory epithelium, aging reduces the capacity for tissue homeostasis and regeneration. The microvillous cell subtype that expresses both inositol trisphosphate receptor type 3 (IP3R3) and the neuroproliferative factor neuropeptide Y (NPY) is critical for regulation of homeostasis, yet its role in aging is undefined.

An IP3R3- and NPY-expressing microvillous cell mediates tissue homeostasis and regeneration in the mouse olfactory epithelium.

Calcium-dependent release of neurotrophic factors plays an important role in the maintenance of neurons, yet the release mechanisms are understudied. The inositol triphosphate (IP3) receptor is a calcium release channel that has a physiological role in cell growth, development, sensory perception, neuronal signaling and secretion. In the olfactory system, the IP3 receptor subtype 3 (IP3R3) is expressed exclusively in a microvillous cell subtype that is the predominant cell expressing neurotrophic factor neuropeptide Y (NPY).

Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium.

Background: ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s) by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices.

Neuropeptide Y and extracellular signal-regulated kinase mediate injury-induced neuroregeneration in mouse olfactory epithelium.

In the olfactory epithelium (OE), injury induces ATP release, and subsequent activation of P2 purinergic receptors by ATP promotes neuroregeneration by increasing basal progenitor cell proliferation. The molecular mechanisms underlying ATP-induced increases in OE neuroregeneration have not been established. In the present study, the roles of neuroproliferative factors neuropeptide Y (NPY) and fibroblast growth factor 2 (FGF2), and p44/42 extracellular signal-regulated kinase (ERK) on ATP-mediated increases of neuroregeneration in the OE were investigated.

ATP mediates neuroprotective and neuroproliferative effects in mouse olfactory epithelium following exposure to satratoxin G in vitro and in vivo.

Intranasal aspiration of satratoxin G (SG), a mycotoxin produced by the black mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) in mouse olfactory epithelium (OE) through unknown mechanisms. Here, we show a dose-dependent induction of apoptosis 24 h post-SG exposure in vitro as measured by increased activated caspases in the OP6 olfactory placodal cell line and increased propidium iodide staining in primary OE cell cultures. Intranasal aspiration of SG increased TUNEL (Terminal dUTP Nick End Labeling) staining in the neuronal layer of the OE and significantly increased the latency to find a buried food pellet, confirming that SG selectively induces neuronal apoptosis and demonstrating that SG impairs the sense of smell.

ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor α in neonatal and adult mice: effect on neuroproliferation.

Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium (OE); however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice.

User-centered design and evaluation of a next generation fixed-split ergonomic keyboard.

Objective: Research has shown that fixed-split, ergonomic keyboards lessen the pain and functional status in symptomatic individuals as well as reduce the likelihood of developing musculoskeletal disorders in asymptomatic typists over extended use. The goal of this study was to evaluate design features to determine whether the current fixed-split ergonomic keyboard design could be improved.

Participants: Thirty-nine, adult-aged, fixed-split ergonomic keyboard users were recruited to participate in one of three studies.

One century of hydrological monitoring in two small catchments with different forest coverage.

Long-term data on precipitation and runoff are essential to draw firm conclusions about the behavior and trends of hydrological catchments that may be influenced by land use and climate change. Here the longest continuous runoff records from small catchments (<1 km(2)) in Switzerland (and possibly worldwide) are reported. The history of the hydrological monitoring in the Sperbel- and Rappengraben (Emmental) is summarized, and inherent uncertainties in the data arising from the operation of the gauges are described.

Microvillous cells expressing IP3 receptor type 3 in the olfactory epithelium of mice.

Microvillous cells of the main olfactory epithelium have been described variously as primary olfactory neurons, secondary chemosensory cells or non-sensory cells. Here we generated an IP3R3(tm1(tauGFP)) mouse in which the coding region for a fusion protein of tau and green fluorescent protein replaces the first exon of the Itpr3 gene. We provide immunohistochemical and functional characterization of the cells expressing IP3 receptor type 3 in the olfactory epithelium.

NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium.

In the CNS, ATP is released upon injury and promotes neuroproliferation via purinergic receptors. In the olfactory epithelium, ATP promotes the synthesis and release of neurotrophic factor NPY in neonates and induces neuroproliferation in neonatal and adult mice. We tested the hypothesis that NPY is involved in ATP-induced neuroproliferation in adult mice olfactory epithelium.

Nickel sulfate induces location-dependent atrophy of mouse olfactory epithelium: protective and proliferative role of purinergic receptor activation.

Exposure to nickel sulfate (NiSO(4)) leads to impaired olfaction and anosmia through an unknown mechanism. We tested the hypothesis that ATP is released following NiSO4-induced injury and that ATP promotes regenerative cell proliferation in the olfactory epithelium (OE). Male Swiss Webster mice were intranasally instilled with NiSO(4) or saline followed by ATP, purinergic receptor antagonists, or saline.

Design and evaluation of a curved computer keyboard.

Conventional, straight keyboards remain the most popular design among keyboards sold and used with personal computers despite the biomechanical benefits offered by alternative keyboard designs. Some typists indicate that the daunting medical device-like appearance of these alternative 'ergonomic' keyboards is the reason for not purchasing an alternative keyboard design. The purpose of this research was to create a new computer keyboard that promoted more neutral postures in the wrist while maintaining the approachability and typing performance of a straight keyboard.

Activation of purinergic receptors induces proliferation and neuronal differentiation in Swiss Webster mouse olfactory epithelium.

In the central nervous system (CNS), adenosine 5'-triphosphate (ATP) induces the synthesis and release of neurotrophic factors, cell proliferation, and differentiation. The olfactory system is one site where multipotent progenitor cells continue to proliferate and differentiate into neurons throughout life. We tested the hypothesis that ATP initiates proliferation in olfactory epithelium by measuring 5-bromo-2-deoxyuridine incorporation.

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome.

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported.

Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.

One premise regarding the mechanism of injury-evoked neuroregeneration is that injured cells induce the release of neurotrophic factors to trigger neurogenesis. Extracellular purine nucleotides exert multiple neurotrophic actions in the central nervous system mediated via activation of purinergic receptors. However, whether purinergics have a neurotrophic role in the olfactory neuroepithelium has not been investigated.

Calcium store-mediated signaling in sustentacular cells of the mouse olfactory epithelium.

Sustentacular cells have structural features that allude to functions of secretion, absorption, phagocytosis, maintenance of extracellular ionic gradients, metabolism of noxious chemicals, and regulation of cell turnover. We present data detailing their dynamic activity. We show, using a mouse olfactory epithelium slice model, that sustentacular cells are capable of generating two types of calcium signals: intercellular calcium waves where elevations in intracellular calcium propagate between neighboring cells, and intracellular calcium oscillations consisting of repetitive elevations in intracellular calcium confined to single cells.

Satratoxin G-induced apoptosis in PC-12 neuronal cells is mediated by PKR and caspase independent.

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, a mold suggested to play an etiologic role in damp building-related illnesses. Acute intranasal exposure of mice to SG specifically induces apoptosis in olfactory sensory neurons of the nose. The PC-12 rat pheochromocytoma cell model was used to elucidate potential mechanisms of SG-induced neuronal cell death.

Purinergic receptor antagonists inhibit odorant-induced heat shock protein 25 induction in mouse olfactory epithelium.

Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, and odorants. Ischemic, stressed, and injured cells release ATP in large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the release of ATP in the olfactory epithelium (OE).

Electrical coupling in sustentacular cells of the mouse olfactory epithelium.

Sustentacular cells (SCs) line the apical surface of the olfactory epithelium (OE) and provide trophic, metabolic, and mechanical support for olfactory receptor neurons. Morphological studies have suggested that SCs possess gap junctions, although physiological evidence for gap junctional communication in mammalian SCs is lacking. In the present study we investigated whether coupling exists between SCs situated in tissue slices of OE from neonatal (P0-P4) mice.

Ionic conductances in sustentacular cells of the mouse olfactory epithelium.

The electrical properties of sustentacular cells (SCs) in the olfactory epithelium (OE) were investigated in tissue slices taken from neonatal mice (P0-P4). Conventional whole-cell recordings were obtained from SCs and also from olfactory receptor neurones (ORNs) in situ. SCs had a larger apparent cell capacitance (C(cell)) (18.

Dopamine reduces odor- and elevated-K(+)-induced calcium responses in mouse olfactory receptor neurons in situ.

Although D2 dopamine receptors have been localized to olfactory receptor neurons (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in ORNs, dopaminergic modulation of either odor responses or excitability in mammalian ORNs has not previously been demonstrated. We found that <50 microM dopamine reversibly suppresses odor-induced Ca2+ transients in ORNs. Confocal laser imaging of 300-microm-thick slices of neonatal mouse olfactory epithelium loaded with the Ca(2+)-indicator dye fluo-4 AM revealed that dopaminergic suppression of odor responses could be blocked by the D2 dopamine receptor antagonist sulpiride (<500 microM).