1,721,066 research outputs found

    Transcriptional regulatory network during development in the olfactory epithelium

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    Regeneration, a process of reconstitution of the entire tissue, occurs throughout life in the olfactory epithelium (OE). Regeneration of OE consists of several stages: proliferation of progenitors, cell fate determination between neuronal and non-neuronal lineages, their differentiation and maturation. How the differentiated cell types that comprise the OE are regenerated, is one of the central questions in olfactory developmental neurobiology. The past decade has witnessed considerable progress regarding the regulation of transcription factors (TFs) involved in the remarkable regenerative potential of OE. Here, we review current state of knowledge of the transcriptional regulatory networks that are powerful modulators of the acquisition and maintenance of developmental stages during regeneration in the OE. Advance in our understanding of regeneration will not only shed light on the basic principles of adult plasticity of cell identity, but may also lead to new approaches for using stem cells and reprogramming after injury or degenerative neurological diseases.1

    Odor habituation can modulate very early olfactory event-related potential

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    Odor habituation is a phenomenon that after repeated exposure to an odor, is characterized by decreased responses to it. The central nervous system is involved in odor habituation. To study odor habituation in humans, measurement of event-related potentials (ERPs) has been widely used in the olfactory system and other sensory systems, because of their high temporal resolution. Most previous odor habituation studies have measured the olfactory ERPs of (200–800) ms. However, several studies have shown that the odor signal is processed in the central nervous system earlier than at 200 ms. For these reasons, we studied whether when odors were habituated, olfactory ERP within 200 ms of odors could change. To this end, we performed an odor habituation behavior test and electroencephalogram experiments. In the behavior test, under habituation conditions, odor intensity was significantly decreased. We found significant differences in the negative and positive potentials within 200 ms across the conditions, which correlated significantly with the results of the behavior test. We also observed that ERP latency depended on the conditions. Our study suggests that odor habituation can involve the olfactory ERP of odors within 200 ms in the brain. © 2020, The Author(s).1

    Timely inhibitory circuit formation by Abl1 regulates innate olfactory behaviors in the mouse

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    Over half of the interneurons in the mouse olfactory bulb (OB) are developed during the first week after birth, and dominantly connect to excitatory tufted cells near the superficial granule cell layer (sGCL), unlike late-born interneurons. However, the molecular mechanisms underlying the temporal specification have not been identified. Here, we discover the role of Abelson Tyrosine-Protein Kinase 1 (Abl1) in the temporal development of early-born OB interneurons. Lentiviral knockdown of Abl1 disrupts sGCL-specific circuit of the early-born interneurons by integratory and functional defects, resulting in olfactory hyper-sensitivity. From a proteomics approach, we find that Doublecortin (Dcx) is phosphorylated by Abl1, and which contributes to the stabilization of Dcx, thereby regulating microtubule dynamics. Finally, Dcx overexpression rescues Abl1-knockdown-induced anatomic or functional defects. In summary, we suggest that the specific signaling of Abl1-Dcx in early-born interneurons facilitates the temporal development of sGCL circuit for regulating innate olfactory functions, such as detection and sensitivity.1

    Early olfactory event related potential can represent odor habituation

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    Habituation is a process showing a decrease in response to a stimulus after being repeatedly exposed to it. To study habituation, measurement of event-related potentials (ERP) has been widely used in the olfactory system as well as other sensory systems. According to previous odor habituation studies, ERP near 200–700 ms was mostly studied. However, several studies showed that odor signal in the central nervous system (CNS) processed earlier than 200 ms. For these reasons, we studied whether early olfactory ERP within 200 ms may be changed during odor habituation. To verify the change of early ERP during odor habituation, we performed an odor habituation behavior test and EEG experiments. The experimental procedure was consisted of three steps. In first step, odorants or distilled water were offered continuously during 30 s. Next, one of two odorants was offered during 2 s for measurement. Last step was 30 s of rest period. There were three different conditions for studying odor habituation: ‘none’ (distilled water offered in first step), ‘different’ (two different odorants offered in first and second step) and ‘same’ (the same odorant offered in first and second step). The perceived intensity was significantly decreased under the same condition compared to those under other conditions in the behavior test. In accordance with behavior results, we found channels showing significantly different ERP amplitude across the conditions and significantly correlated with the behavior test within 200 ms. These results suggest that early ERP signal of the brain may be involved in odor habituation as other sensory systems, and that odor habituation was processed differently depending on brain areas. Our studies suggest that odor habituation may be represented by the change of early negative potential in the brain and these processes may be different depending on brain areas.1

    A study of visual-olfactory interactions using context-related smell

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    As attempts combining movies with smell have been increased in movie industries, interest of visual-olfactory cross-modal studies has been increased. According to previous studies, high congruency condition by odors could modulate perceptual responses of visual stimulation and neural activities as well. However there were limited evidences regarding perceptual response to visual stimulation with context-related smell. These evidences may be crucial to screening cheaper and safe odorants with evoking similar perceptual effects. Therefore, we studied how context-related smell may affect the perceptual responses to visual stimulation. To understand effects of context-related smell, we performed questionnaires and EEG studies. For the visual stimulation, two video clips were used: high valence and low valence. Four odorants were used in this experiment: lavender, geranial, 2-furanmethanethiol and 2-ethyl-3,5-dimethylpyrazine. Odorants were divided into two categories: category A (lavender, geranial) and category B (2-furanmethanethiol, 2-ethyl-3,5-dimethylpyrazine) by structural similarity. Odorants were offered with a video clip simultaneously during measuring about 10 s. There were 53 participants (27 men, 26 women) divided into 4 group depending on category conditions. We found that context-related smell induced similar congruency with video clips. As predicted, proper match between the smell and videos showed high congruency. In our EEG studies, alpha asymmetry was changed depending on odor category and congruency only in low valence video clips. High valence video clips did not show similar results as low valence video clips. Taken together, our studies suggested that context-related smell can induce different brain activities, although their behavioral outcomes were similar in video clips.1

    cIAP1 may be involved in survival of the olfactory system

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    Maintenance of neurons is regulated by various factors from in the molecular manner to the systemic manner. And external and internal environmental cues also modulate the maintenance of neurons. In this process, neurons are exposed to the stimuli and can easily get stressed, and which leads to neuronal death and impairs to establishment of their connections and activities. As a representative sensory system, the peripheral olfactory system is directly exposed to the environment to detect the external stimuli. Volatile molecules or natural gas in the air are detected by the olfactory sensory neurons (OSNs) in the olfactory epithelium (OE), and the OSNs are connected to the central nervous system (CNS) via the olfactory bulb (OB). Constant exposure to external stimuli may cause damages to the OSNs, and which in turn afflicts to acute or chronic diseases like olfactory impairment, chronic rhinitis, etc. Inhibitor of apoptosis proteins (IAPs) interact with caspases and inhibit apoptosis. In particular, cIAP1 is one of the regulators of NF-κB (nuclear factor kappa-light-chain-enhancer of B cells) activation and TNF (tumor necrosis factor) signals, which is crucial for inflammatory responses. Although there were several studies related to the cell death of the olfactory system caused by external stimuli, the mechanisms and the role of cIAP1 in the olfactory system has not been fully understood. To this end, cIAP1 KO mice were studied to identify the critical roles of cIAP1 in the olfactory system. Behavioral assay demonstrated that cIAP1 deprivation caused smell dysfunction. Moreover, the numbers of OSNs in the OE was decreased and the thickness of the OE was observed thinner compared to WT animals. In summary, cIAP1 may play important roles for OSN survival.1

    Development of Alzheimer's disease biomarker using Aβ* 56 soluble oligomer in human nasal secretions

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    Background: Although soluble Aβ oligomer (AβO) might play a pivotal role in pathogenesis of Alzheimer's disease (AD), development of biomarker using detection of AβO might be limited due to its structural heterogeneity. Recently, we found the 56kDa soluble Aβ*56(Aβ*56) which is known to be involved in a very early sate of AD in human nasal secretion. The aim of this study is to explore diagnostic validity of Aβ*56 in nasal secretions in discriminating AD pathology. Method: A total of 28 patients (normal control (NC) = 9, amnestic mild cognitive impairment (aMCI) = 10, and AD = 9) were included in the study. They were dichotomized using 18F-Flutemetamol amyloid positron emission tomography (PET) into with and without detectable amyloid burden. Level of Aβ*56 in nasal secretions were measured using immune blotting. Group differences in nasal Aβ*56 level were analyzed and correlation between nasal Aβ*56 level and mean standardized uptake value ratio were also conducted. Result: There were no group differences in age, gender, and education. The nasal Aβ*56 level were significantly higher in aMCI and AD than NC group, but no group differences were found between aMCI and dementia. The nasal Aβ*56 level also had a positive correlation with cortical Aβ deposition on 18F-Flutemetamol PET. Conclusion: These results demonstrate that the nasal Aβ*56 level can be easily measured, and it may be utilized as a biomarker for the diagnosis of early AD including aMCI. The study also suggests that nasal Aβ*56 level may predict cortical deposition of Aβ.1

    Odor quality profile is partially influenced by verbal cues

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    Characterizing an odor quality is difficult for humans. Ever-increasing physiological and behavioral studies have characterized odor quality and demonstrated high performance of human odor categorization. However, there are no precise methods for measuring the multidimensional axis of an odor quality. Furthermore, it can be altered by individual experience, even when using existing measurement methods for the multidimensional axis of odor such as odor profiling. It is, therefore, necessary to characterize patterns of odor quality with odor profiling and observe alterations in odor profiles under the influence of subjective rating conditions such as verbal cues. Considering the high performance of human odor categorization, we hypothesized that odor may have specific odor quality that is scarcely altered by verbal cues. We assessed odor responses to isovaleric acid with and without verbal cues and compared the results in each stimulation condition. We found that verbal cues influenced the rating of odor quality descriptors. Verbal cues weakly influenced the odor quality descriptors of high-rated value (upper 25%) compared to odor quality descriptors of low-rated value (lower 75%) by the survey test. Even under different verbal cue conditions, the same odor was classified in the same class when using high-rated odor quality descriptors. Our study suggests that people extract essential odor quality descriptors that represent the odor itself in order to efficiently quantify odor quality.</div

    Neurobiology and Cultivation of Olfactory Receptor Neurons on a Chip

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    The continued study of the olfactory system is essential, as elucidation of its molecular, cellular, and systems neurobiology will undoubtedly reveal a complex interplay that transduces odorant molecule-induced action potentials into odor information processes in the brain such as the mediation of emotion, memory and behavior. Additionally, interest in the olfactory system and its potential applications in the industrial and engineering fields continue to increase. In this chapter, we describe various aspects of olfactory cells ranging from their cellular structures and functions to the development of olfactory cell cultivation methods and the application of cultivated olfactory cells and bio-engineered cells to various types of bioelectronic devices. These applications may ultimately facilitate the development of biomimetic artificial noses. © 2014 Springer Science+Business Media Dordrecht.1
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