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

Purinergic nucleotides, including ATP and adenosine, are important neuromodulators of peripheral auditory visual sensory systems (Thorne Housley, 1996). released by the olfactory epithelium (OE) after noxious stimuli provides a physiological source for neuromodulatory substance independent efferent innervation. Here we show that multiple subtypes purinergic receptors differentially expressed in receptor neurons sustentacular support cells. Activation evoked inward currents increases...

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

Exposure to nickel sulfate (NiSO4) leads impaired olfaction and anosmia through an unknown mechanism. We tested the hypothesis that ATP is released following NiSO4-induced injury promotes regenerative cell proliferation in olfactory epithelium (OE). Male Swiss Webster mice were intranasally instilled with NiSO4 or saline followed by ATP, purinergic receptor antagonists, saline. assessed for changes using histology immunohistochemistry 1–7 days postinstillation compared results bulb...

Abstract Microvillous cells of the main olfactory epithelium have been described variously as primary neurons, secondary chemosensory or non‐sensory cells. Here we generated an IP3R3 tm1(tauGFP) mouse in which coding region for a fusion protein tau and green fluorescent replaces first exon Itpr3 gene. We provide immunohistochemical functional characterization expressing IP3 receptor type 3 epithelium. These bear microvilli at their apex, therefore termed them MV The cell body these lies...

The electrical properties of sustentacular cells (SCs) in the olfactory epithelium (OE) were investigated tissue slices taken from neonatal mice (P0-P4). Conventional whole-cell recordings obtained SCs and also receptor neurones (ORNs) situ. had a larger apparent cell capacitance (C(cell)) (18.6 +/- 0.5 pF) than ORNs (4.4 0.4 lower membrane resistance (R(m)) (160 11 MOmega versus 664 195 MOmega, respectively). When corrected for seal 1 GOmega, these mean R(m) values increased to 190 2 GOmega...

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

The B-chemokine RANTES has recently been implicated in the neuropathogenesis of human immunodefiency virus. Based upon previous studies effects morphine on microglial cell production cytokines and chemotaxis towards activated complement component C5a, we tested hypothesis that this opiate would alter migration by microglia. Treatment highly purified cultures with (10 –8 –10 –6 M) potently inhibited lipopolysaccharide-and interleukin-1[.beta]-stimulated cells. Using a chamber to assess...

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

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

Abstract Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, odorants. Ischemic, stressed, injured release ATP large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the olfactory epithelium (OE). Extracellular ATP, signal cellular induces expression HSPs via purinergic receptors. In present study, vivo odorant exposure (heptanal or R ‐carvone)...

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

Abstract One premise regarding the mechanism of injury‐evoked neuroregeneration is that injured cells induce release neurotrophic factors to trigger neurogenesis. Extracellular purine nucleotides exert multiple actions in central nervous system mediated via activation purinergic receptors. However, whether purinergics have a role olfactory neuroepithelium has not been investigated. Thus, we monitored ATP‐induced neuropeptide Y (NPY), increases neuroproliferation epithelium. To visualize NPY...

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, mold suggested to play an etiologic role in damp building-related illnesses. Acute intranasal exposure of mice SG specifically induces apoptosis olfactory sensory neurons the nose. The PC-12 rat pheochromocytoma cell model was used elucidate potential mechanisms SG-induced neuronal death. Agarose gel electrophoresis revealed that at 10 ng/ml or higher for 48-h induced DNA fragmentation...

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

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 regulation mouse epithelium. In vivo proliferation cell lineage studies were performed mice (C57BL/6 cannabinoid type 1 2 receptor deficient strains) treated with directly (WIN 55,212–2 or 2-arachidonylglycerol ether) indirectly via inhibition hydrolytic enzymes. Cannabinoids increased...

Abstract In adult olfactory epithelium (OE), ATP plays a role in constant cell turnover and post-injury neuroregeneration. We previously demonstrated that constitutive ATP-evoked release are present neonatal mouse OE underlie continuous turn-over neuroregeneration, activation of purinergic P2X 7 receptors is involved the evoked release. hypothesized both releases OE. To study putative contribution sensory neurons to release, we used neuronal-like OP6 cells derived from embryonic placode...