• A 26-year-old woman had an 8-year history of phantosmia in her left nostril. The phantosmia could be eliminated by nostril occlusion or cocainization of the olfactory epithelium on the involved side. Because her symptoms and testing suggested a peripheral problem, a full-thickness "plug" of olfactory epithelium from under the cribriform plate (including all the fila olfactoria) was excised. At 5 weeks postoperatively, the phantosmia was completely gone, and her olfactory ability had returned to preoperative levels. Either the removal of abnormal peripheral olfactory neurons from the nose or the interruption of incoming signals to the olfactory bulb eliminated the phantosmia. This form of therapy for phantosmia offers an alternative to more radical procedures such as olfactory bulbectomy and may offer a significant sparing of olfactory ability. (Arch Otolaryngol Head Neck Surg. 1991;117:1402-1406)
We provide a review of Spectrin isoform function in the cytoplasm, the nucleus, the cell surface, and in intracellular signaling. We then discuss the importance of Spectrin’s E2/E3 chimeric ubiquitin conjugating and ligating activity in maintaining cellular homeostasis. Finally we present spectrin isoform subunit specific human diseases. We have created the Spectrinome, from the Human Proteome, Human Reactome and Human Atlas data and demonstrated how it can be a useful tool in visualizing and understanding spectrins myriad of cellular functions. Impact statement Spectrin was for the first 12 years after its discovery thought to be found only in erythrocytes. In 1981, Goodman and colleagues 1 found that spectrin-like molecules were ubiquitously found in non-erythroid cells leading to a great multitude of publications over the next thirty eight years. The discovery of multiple spectrin isoforms found associated with every cellular compartment, and representing 2-3% of cellular protein, has brought us to today’s understanding that spectrin is a scaffolding protein, with its own E2/E3 chimeric ubiquitin conjugating ligating activity that is involved in virtually every cellular function. We cover the history, localized functions of spectrin isoforms, human diseases caused by mutations, and provide the spectrinome: a useful tool for understanding the myriad of functions for one of the most important proteins in all eukaryotic cells.
The social transmission of food preference paradigm centers on the finding that observers obtain dietary information through olfactory cues on the breath of a demonstrator peer that has ingested a novel substance. This phenomenon plays a role in ethanol acceptability. Historically, studies using this technique have focused on observer animals in order to study the social transmission process. With respect to ethanol, studies of acute intoxication have shown that the pharmacologic properties of ethanol and hematogenic olfaction can influence the subsequent ethanol odor-mediated responses of the intoxicated animals. These acute studies, however, demonstrate odor aversion. The present study compared the effect of adolescent ethanol exposure, via the social transmission paradigm, on the behavioral response to ethanol odor in both observer and demonstrator animals in adolescence (postnatal day (P) 37) and the persistence of these effects into adulthood (P90).Beginning on P29, naïve rats received four ethanol or water exposures: one every 48 hours through either direct intragastric infusion or social interaction with an infused peer. The reflexive sniffing response of observers and demonstrators to ethanol odor was tested at P37 or P90 using whole-body plethysmography.The behavioral response of adolescent ethanol observers and demonstrators significantly differed between themselves and from their respective water controls. Ethanol and water observers both displayed a greater response to ethanol odor than their respective demonstrator counterparts. Compared to controls, both modes of ethanol exposure produced similar magnitudes of enhancement. At P90, both forms of exposure displayed similar responses to ethanol odor and similar magnitudes of enhancement. Only demonstrators displayed equivalent enhanced responses in both sexes.In contrast to previous studies showing odor aversion following acute ethanol intoxication, within the context of the social transmission paradigm, adolescent demonstrators like observers showed an enhanced behavioral response to ethanol odor. The differential enhanced odor response between observers and demonstrators, despite similar net enhancements relative to controls, suggests the presence of a stress effect from the infusion technique. This finding contrasts previous suggestions that intragastric infusions create minimal stress: an important consideration when conducting ethanol research. This stress effect appears to ameliorate by adulthood.
1. Fluorescence changes in the dye di-4-ANEPPS were monitored on the rat's nasal septum and medial surface of the turbinates in response to odorant stimuli. For each mucosal surface a 6.0 x 6.0-mm area was sampled at 100 contiguous sites with a 10 x 10 photodiode array. The odorants were propyl acetate, 2-propanol, citral, L-carvone and ethylacetoacetate, each presented at a low and high concentration. 2. Like previous work using optical recording techniques and potential-sensitive dyes on the amphibian epithelium, the fluorescence signals elicited by odorant stimuli in the rat preparation were nearly identical in shape, time course, and response characteristics as the electroolfactogram (EOG). As with the EOG, a response could only be recorded in the presence of odorant stimuli (that is, no response was detected when nonodorized, humidified air was presented as the stimulus); the amplitude depended on odorant concentration, and the response was abolished both by ether and Triton X-100. 3. Although the entire expanse of each sampled tissue (i.e., septum and medial surface of the turbinates) responded to stimulation with each odorant, each stimulus induced a distinct spatial pattern of activity that was independent of odorant concentration and consistent from animal to animal. Furthermore, the spatial activity patterns recorded for the septum were mirror images of those recorded from the medial surface of the turbinates. 4. Formal statistical analysis of the loci of maximal activity or "hot spot" indicated highly significant effects of the odorants for both the septum and medial surface of the turbinates. 5. The results of these studies give further support to the hypothesis that odorant quality is encoded by differential spatial activity patterns in the olfactory epithelium that are characteristic of different odorants.
The present study assessed the functional consequences of viral infection with a neurotropic coronavirus, designated MHV OBLV, that specifically targets central olfactory structures. Using standard operant techniques and a `go, no-go' successive discrimination paradigm, six BALB/c mice were trained to discriminate between the presentation of an air or odor stimulus (three mice for each of the odorants propanol and propyl acetate). Two additional BALB/c mice were trained to discriminate between the presentation of air and the presentation of either vanillin or propionic acid. Following criterion performance, each mouse received an additional 2000 trials of overtraining. At completion of overtraining one mouse from the propanol and propyl acetate groups were allocated as untreated. The remaining six mice were inoculated with 300 μl of the OBLV stock per nostril for a total of 1.5 × 106 p.f.u. in 600 μl. Following a 1 month rest, untreated and inoculated animals were again tested on their respective air versus odor discrimination task. Untreated animals immediately performed at criterion levels. In contrast, inoculated animals varied in their capacity to discriminate between air and odorant. Five of the six inoculated mice showed massive disruption of the olfactory bulb, including death of mitral cells; the other was more modestly affected. In addition, the density of innervation of the olfactory mucosa by substance P-containing trigeminal fibers is also affected by inoculation. Those mice that remained anosmic to the training odorants had the most severe reduction in mitral cell number and substance P fiber density among the inoculated animals.
Abstract Olfactory epithelium retains the capacity to recover anatomically after damage well into adult life and perhaps throughout its duration. None the less, olfactory dysfunctions have been reported widely for elderly humans. The present study investigates the effects of aging on the neurophysiological and anatomical status of the olfactory epithelium in barrier‐raised Fischer 344X Brown Norway F 1 hybrid rats at 7, 10, 25 and 32/35 months old. The posterior part of the olfactory epithelium in 32/35‐month‐old rats is well preserved. Globose basal cells are dividing, and new neurons are being born even at this advanced age. None the less, the numbers of proliferating basal cells and immature, GAP‐43 (+) neurons are significantly decreased. Neurophysiological status was evaluated using voltage‐sensitive dye techniques to assess inherent patterns of odorant‐induced activity in the epithelium lining the septum and the medial surface of the turbinates. In middle and posterior zones of the epithelium, there were neither age‐related changes in overall responsivity of this part of the olfactory epithelium to any of five odorants, nor shifts in the location of the odorant‐induced hotspots. The inherent activity patterns elicited by the different odorants do become more distinct as a function of age, which probably reflects the decline in immature neurons and a slight, but not statistically significant, increase in mature neurons as a function of age. In contrast with the excellent preservation of posterior epithelium, the epithelium lining the anterodorsal septum and the corresponding face of the turbinates is damaged in the 32/35‐month‐old animals: in this part, horizontal basal cells are reactive, more basal cells and sustentacular cells are proliferating than in younger animals or in posterior epithelium of the same animals, and the neuronal population is less mature on average. Our findings indicate that degeneration of the olfactory epithelium is not an inevitable or pre‐programmed consequence of the aging process, since the posterior zone of the epithelium is very well preserved in these barrier‐protected animals. However, the deterioration in the anterior epithelium suggests that environmental insults can accumulate or become more severe with age and overwhelm the regenerative capacity of the epithelium. Alternatively, the regenerative capacity of the epithelium may wane somewhat with age. Either of these mechanisms or some combination of them can account for the functional and anatomical deterioration of the sense of smell associated with senescence in humans.
