Biomedical subjects

Nancy E Rawson

Publications and source records attributed to Nancy E Rawson.

10 recordsLinked to original sources

PubMed2006

Olfactory loss in aging.

Olfactory loss is a common age-related complaint that may be caused by changes in the anatomy of the structures required for olfaction (for example, loss of olfactory receptor cells) or in the environment surrounding the receptor cell (for example, altered nasal mucus composition). However, aging, as well as age-related diseases and medications, may also alter the distribution, density, or function of specific receptor proteins, ion channels, or signaling molecules that affect the ability of neural elements throughout the olfactory pathway to signal and process odorant information. Although a great deal has been learned about the prevalence and nature of age-related olfactory loss, we are just beginning to explore avenues to prevent or alleviate this sensory deficit. Some studies suggest that, rather than being a necessary outcome of aging, age-associated factors such as chronic diseases, medications, and dental and sinus problems are the primary culprits in causing olfactory impairment. This idea suggests optimism in that, as we address these other age-related health issues, the prevalence of olfactory loss will lessen as well.

Aged↗

PubMed2006

Characterization and long-term maintenance of rat taste cells in culture.

Taste cells have a limited life span and are replaced from a basal cell population, although the specific factors involved in this process are not well known. Short- and long-term cultures of other sensory cells have facilitated efforts to understand the signals involved in proliferation, differentiation, and senescence, yet few studies have reported successful primary culture protocols for taste cells. Furthermore, no studies have demonstrated both proliferation and differentiation in vitro. In this study, we have developed an in vitro culture system to maintain and utilize rat primary taste cells for more than 2 months without losing key molecular and biochemical features. Gustducin, phospholipase C-beta2 (PLC-beta2), T1R3, and T2R5 mRNA were detected in the cultured cells by reverse transcriptase-polymerase chain reaction. Western blot analysis demonstrated gustducin and PLC-beta2 expression in the same samples, which was confirmed by immunocytochemistry. Labeling with bromo-2-deoxyuridine (BrdU) demonstrated proliferation, and a subset of BrdU-labeled cells were also immunoreactive for either gustducin or PLC-beta2, indicating differentiation of newly generated cells in vitro. Cultured cells also exhibited increases in intracellular calcium in response to several taste stimuli. These results indicate that taste cells from adult rats can be generated and maintained under the described conditions for at least 2 months. This system will enable further studies of the processes involved in proliferation, differentiation, and function of mammalian taste receptor cells in an in vitro preparation.

Animals↗

PubMed2006

Transduction and coding.

Odor transduction and quality coding involves a cascade of events that occur at the level of the olfactory epithelium and olfactory bulbs. Odorants bind to one or a few specific olfactory receptors located in the cilia of olfactory neurons. These olfactory receptor proteins make up the largest gene family discovered and are diverse between and within species. The change of chemical signals to neural signals in the olfactory neurons involves G-coupled proteins and the cascade of second messenger pathways that open ion channels to depolarize the cell and trigger a series of action potentials carried along the receptor cell axon resulting in release of glutamate at synapses with mitral cells within the olfactory bulb. These neural signals in the olfactory bulb produce unique odor maps that play an important role in our ability to detect and discriminate thousands of different odorants. The olfactory neurons are replaced throughout life from a population of slowly dividing basal cells within the epithelium. Disease, infection, injury or aging can interfere with neuronal cell replacement as well as transduction and coding processes, resulting in impairment and distortions of olfactory performance.

Aging↗

PubMed2005

Evidence for multiple calcium response mechanisms in mammalian olfactory receptor neurons.

Olfactory receptor neurons employ a diversity of signaling mechanisms for transducing and encoding odorant information. The simultaneous activation of subsets of receptor neurons provides a complex pattern of activation in the olfactory bulb that allows for the rapid discrimination of odorant mixtures. While some transduction elements are conserved among many species, some species-specificity occurs in certain features that may relate to their particular physiology and ecological niche. However, studies of olfactory transduction have been limited to a relatively small number of vertebrate and invertebrate species. To better understand the diversity and evolution of olfactory transduction mechanisms, we studied stimulus-elicited calcium fluxes in olfactory neurons from a previously unstudied mammalian species, the domestic cat. Isolated cells from cat olfactory epithelium were stimulated with odorant mixtures and biochemical agents, and cell responses were measured with calcium imaging techniques. Odorants elicited either increases or decreases in intracellular calcium; odorant-induced calcium increases were mediated either by calcium fluxes through the cell membrane or by mobilization of intracellular stores. Individual cells could employ multiple signaling mechanisms to mediate responses to different odorants. The physiological features of these olfactory neurons suggest greater complexity than previously recognized in the role of peripheral neurons in encoding complex odor stimuli. The investigation of novel and unstudied species is important for understanding the mechanisms of odorant signaling that apply to the olfactory system in general and suggests both broadly conserved and species-specific evolutionary adaptations.

Animals↗

PubMed2005

In vivo and in vitro neurogenesis in human olfactory epithelium.

The birth and differentiation of neurons have been extensively studied in the olfactory epithelium (OE) of rodents but not in humans. The goal of this study was to characterize cellular composition and molecular expression of human OE in vivo and in vitro. In rodent OE, there are horizontal basal cells and globose basal cells that are morphologically and functionally distinct. In human OE, however, there appears to be no morphological distinction among basal cells, with almost all cells having round cell bodies similar to rodent globose basal cells. Unlike the case in rodents, human basal cells, including putative neuronal precursors, express p75NGFR, suggesting a distinctive role for p75NGFR in human OE neurogenesis. Molecular expression of neuronal cells during differentiation in human OE grossly follows that in rodents. However, the topographical organization of immature and mature ORNs in human OE differs from that of rodents, in that immature and mature ORNs in humans are dispersed throughout the OE, whereas rodent counterparts have a highly laminar organization. These observations together suggest that the birth and differentiation of neuronal cells in human OE differ from those in rodents. In OE explant culture, neuronal cells derived from human OE biopsy express markers for immature and mature neurons, grossly recapitulating neuronal differentiation of olfactory neurons in vivo. Furthermore, small numbers of cells are doubly label for bromodeoxyuridine and olfactory marker protein, indicating that neuronal cells born in vitro reach maturity. These data highlight species-related differences in OE development and demonstrate the utility of explant culture for experimental studies of human neuronal development.

Adult↗

PubMed2005

Aberrant intracellular calcium signaling in olfactory neurons from patients with bipolar disorder.

OBJECTIVE: The authors examined the feasibility of using olfactory receptor neurons from living patients to test whether calcium signaling is altered in a neuronal cell population in bipolar disorder. METHOD: Ratiometric fluorescence photomicroscopy was used to assess basal and stimulus-induced changes in intracellular calcium levels in biopsy-derived olfactory receptor neurons from seven euthymic patients with bipolar disorder who were medication-free, 10 euthymic patients with bipolar disorder who were treated with mood stabilizers, and 17 age- and sex-matched comparison subjects without bipolar disorder. RESULTS: Olfactory receptor neurons from the seven medication-free patients responded to stimuli predominantly with decreases in intracellular calcium, unlike those from the seven matched healthy subjects. Olfactory receptor neurons from patients treated with mood stabilizers were less likely to respond to stimulation than olfactory receptor neurons from medication-free patients. CONCLUSIONS: This study demonstrates the feasibility of using olfactory receptor neurons to examine alterations in intracellular signaling in neuronal cells from living patients. Our results, although based on a small number of subjects, suggest that altered intracellular calcium signaling in olfactory receptor neurons may be a trait of bipolar disorder.

Anticonvulsants↗

PubMed2003

2,5-Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger stimulus?

To test the hypothesis that decreased hepatocyte ATP is transduced into a hepatic neuronal signal via a change in sodium pump activity, we examined the effect of 2,5-anhydro-D-mannitol (2,5-AM), which stimulates feeding behavior in rats, on intracellular sodium levels using 23Na nuclear magnetic resonance (NMR) spectroscopy. Isolated hepatocytes suspended in agarose beads were superfused with either 2.5 mM 2,5-AM or fructose in the presence of the paramagnetic shift reagent, thulium(III)(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonate)). Superfusion with 2,5-AM decreased hepatocyte ATP and increased intracellular sodium levels compared with superfusion with either fructose or shift reagent alone starting within 15 min of exposure, reaching a maximum level of 120% of baseline by 30 min and declining gradually thereafter over the next 90 min. Superfusion with fructose, which also decreased hepatocyte ATP but by less than half the amount seen with 2,5-AM, had no significant effect on cellular sodium levels. The results support the hypothesis that changes in sodium pump activity could participate in transducing a hunger stimulus associated with hepatocyte energy status into a signal for hunger.

Adenosine Triphosphate↗

PubMed2003

2,5-Anhydro-D-mannitol increases hepatocyte calcium: implications for a hepatic hunger stimulus.

The fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), triggers feeding in rats via a mechanism linked to its ability to trap phosphate and deplete hepatic ATP. This metabolic inhibitor is particularly useful in the study of the role of the liver in initiation of feeding as its effects are preferentially localized to the liver, and its metabolic consequences have been extensively characterized. To determine whether changes in intracellular calcium may participate in a mechanism conveying information about hepatic energy status to the nervous system, we studied the effects of 2,5-AM on intracellular calcium in isolated hepatocytes using the ratiometric indicator, fura-2. 2,5-AM elicited a marked elevation of intracellular calcium within 2-3 min of exposure that returned to baseline upon removal of the agent. Removal of external calcium failed to prevent this response, while emptying intracellular stores prevented it. These data are consistent with the hypothesis that hepatic energy status may be conveyed to the nervous system via a calcium-mediated secretion event.

Animals↗

PubMed2002

Cell and molecular biology of human olfaction.

Progress in our understanding of olfactory receptor physiology has progressed greatly over the past 10 years. It has become clear that many anatomical and molecular features of the peripheral aspect of the olfactory system have remained highly conserved across diverse species. Yet, this structure is responsible for conveying a wide variety of information about the environment that is necessary to the successful location of food, mates, and avoidance of danger, and it is thus not surprising that specializations have also evolved to suit the differing needs of different species. While the basic anatomical features reflect those of other mammals, functional studies of human olfactory receptor neurons have revealed physiological features both similar to and differing from those of other mammalian species. This review presents an overview of both the anatomical and physiological data describing the cell and molecular biology of the peripheral human olfactory system and how it functions in health and disease.

Humans↗

PubMed2002

The superior turbinate as a source of functional human olfactory receptor neurons.

OBJECTIVES: The function of human olfactory receptor neurons (ORNs) remains incompletely understood, in part because of the difficulty of obtaining viable olfactory tissue for study. During endoscopic sphenoidotomy, a portion of the superior turbinate is often removed to achieve wide and safe access to the sphenoid sinus. The purpose of this study was to determine whether functional olfactory mucosa could be obtained from such superior turbinate tissue. STUDY DESIGN/METHODS: Superior turbinate tissue was resected from 4 patients undergoing transnasal endoscopic approaches to the sphenoid sinus. The gross appearance of the turbinate mucosa was normal at the time of surgery. The specimens were placed directly into cold cell culture media and transferred to the laboratory. A portion of the mucosa was fixed and embedded for histology and immunohistochemistry. The remaining tissue was enzymatically dissociated, and the resulting cell suspension was either prepared for immediate calcium imaging or placed into cell culture. Cultured ORNs underwent calcium imaging after several weeks to assess their ability to respond to odorants. RESULTS: Histologic analysis of superior turbinate tissue revealed the presence of patchy olfactory neuroepithelium staining positive for olfactory marker protein. Acutely dissociated ORNs were capable of generating calcium responses to odorant mixtures. ORNs could be maintained in mixed culture and retained their ability to respond to odorants. CONCLUSIONS: Superior turbinate tissue removed during endoscopic sphenoidotomy can provide a valuable source of human olfactory neuroepithelium for functional or histologic study. Superior turbinate tissue yields stem cells and immature neurons capable of differentiating into ORNs that retain many of their functional characteristics even after growth in culture.

Cells, Cultured↗