scholarly journals Expansion of murine and human olfactory epithelium/mucosa colonies and generation of mature olfactory sensory neurons under chemically defined conditions

Theranostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 684-699
Author(s):  
Wenwen Ren ◽  
Li Wang ◽  
Xiujuan Zhang ◽  
Xiaoyu Feng ◽  
Liujing Zhuang ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Olfactory Sensory Neurons

scholarly journals Renewal and Differentiation of GCD Necklace Olfactory Sensory Neurons

2020 ◽  
Vol 45 (5) ◽  
pp. 333-346 ◽  
Author(s):  
Maria Lissitsyna Bloom ◽  
Lucille B Johnston ◽  
Sandeep Robert Datta
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Developmental Trajectory ◽  
Olfactory Sensory Neurons ◽  
Differentiation Process ◽  
Main Olfactory Epithelium ◽  
Horizontal Migration ◽  
Sensory Responses ◽  
And Migration ◽  
Β Tubulin

Abstract Both canonical olfactory sensory neurons (OSNs) and sensory neurons belonging to the guanylate cyclase D (GCD) “necklace” subsystem are housed in the main olfactory epithelium, which is continuously bombarded by toxins, pathogens, and debris from the outside world. Canonical OSNs address this challenge, in part, by undergoing renewal through neurogenesis; however, it is not clear whether GCD OSNs also continuously regenerate and, if so, whether newborn GCD precursors follow a similar developmental trajectory to that taken by canonical OSNs. Here, we demonstrate that GCD OSNs are born throughout adulthood and can persist in the epithelium for several months. Phosphodiesterase 2A is upregulated early in the differentiation process, followed by the sequential downregulation of β-tubulin and the upregulation of CART protein. The GCD and MS4A receptors that confer sensory responses upon GCD neurons are initially expressed midway through this process but become most highly expressed once CART levels are maximal late in GCD OSN development. GCD OSN maturation is accompanied by a horizontal migration of neurons toward the central, curved portions of the cul-de-sac regions where necklace cells are concentrated. These findings demonstrate that—like their canonical counterparts—GCD OSNs undergo continuous renewal and define a GCD-specific developmental trajectory linking neurogenesis, maturation, and migration.

scholarly journals Response of Olfactory Sensory Neurons to Mercury Ions in Zebrafish: An Immunohistochemical Study

2021 ◽  
pp. 1-16
Author(s):  
Maurizio Lazzari ◽  
Simone Bettini ◽  
Liliana Milani ◽  
Maria G. Maurizii ◽  
Valeria Franceschini
Keyword(s):  
Image Analysis ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Basal Layer ◽  
Toxic Metal ◽  
Olfactory Sensory Neurons ◽  
Different Types ◽  
Dividing Cells ◽  
Epithelium Thickness ◽  
Olfactory Rosette

Abstract Olfactory sensory neurons (OSNs) of fish belong to three main types: ciliated olfactory sensory neurons (cOSNs), microvillous olfactory sensory neurons (mOSNs), and crypt cells. Mercury is a toxic metal harmful for olfaction. We exposed the olfactory epithelium of zebrafish to three sublethal Hg2+ concentrations. Molecular markers specific for the different types of OSNs were immunohistochemically detected. Image analysis of treated sections enabled counting of marked cells and measurement of staining optical density indicative of the response of OSNs to Hg2+ exposure. The three types of OSNs reacted to mercury in a different way. Image analysis revealed that mOSNs are more susceptible to Hg2+ exposure than cOSNs and crypt cell density decreases. Moreover, while the ratio between sensory/nonsensory epithelium areas is unchanged, epithelium thickness drops, and dividing cells increase in the basal layer of the olfactory epithelium. Cell death but also reduction of apical processes and marker expression could account for changes in OSN immunostaining. Also, the differential results between dorsal and ventral halves of the olfactory rosette could derive from different water flows inside the olfactory chamber or different subpopulations in OSNs.

scholarly journals Modulation of Spontaneous and Odorant-Evoked Activity of Rat Olfactory Sensory Neurons by Two Anorectic Peptides, Insulin and Leptin

2009 ◽  
Vol 101 (6) ◽  
pp. 2898-2906 ◽  
Author(s):  
Agnès Savigner ◽  
Patricia Duchamp-Viret ◽  
Xavier Grosmaitre ◽  
Michel Chaput ◽  
Samuel Garcia ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Spontaneous Activity ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Signal To Noise Ratio ◽  
Isoamyl Acetate ◽  
Firing Frequency ◽  
Olfactory Sensory Neurons ◽  
Underlying Mechanisms

In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% ( n = 24) and 75.0% ( n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by ∼25% and decreased the interspike intervals by ∼13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status.

scholarly journals Sequential Maturation of Olfactory Sensory Neurons in the Mature Olfactory Epithelium

eNeuro ◽  
2019 ◽  
Vol 6 (5) ◽  
pp. ENEURO.0266-19.2019 ◽  
Author(s):  
Teresa Liberia ◽  
Eduardo Martin-Lopez ◽  
Sarah J. Meller ◽  
Charles A. Greer
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Olfactory Sensory Neurons

scholarly journals Region Specific Amyloid-β Accumulation in Olfactory Sensory Neurons Influences Ecto-Ventral Olfactory Dysfunction in 5xFAD Mice

2020 ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Olfactory System ◽  
Amyloid Β ◽  
Olfactory Dysfunction ◽  
Olfactory Sensory Neurons ◽  
Basal Cells ◽  
Irreversible Damage ◽  
5Xfad Mouse

Abstract Background: Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although the causes of damage have been proposed in every olfactory system including olfactory epithelium, olfactory bulb and olfactory cortex, the main causes of AD- related hyposmia are largely unknown. Methods: We here focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also histologically confirmed the pathological changes in three-month-old 5xFAD mouse models which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of anatomical plane. Results: We observed the odorant group, which 5xFAD mouse could not detect, also neither did physiologically activate the OSNs that propagate to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the ecto-ventrally located OSNs that showed reduced responses to odorants. We also observed irreversible damage to the ecto-region of the olfactory epithelium by measuring impaired neuronal turnover ratio from the basal cells to the matured OSNs. Conclusions: Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely-associated with peripheral OSN’s loss could be a leading cause of the AD-related hyposmia, a characteristic of early AD.

scholarly journals Sox10-dependent neural crest origin of olfactory microvillous neurons in zebrafish

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ankur Saxena ◽  
Brian N Peng ◽  
Marianne E Bronner
Keyword(s):  
Neural Crest ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Cell Tracking ◽  
Function Analysis ◽  
Critical Role ◽  
Primary Source ◽  
Olfactory Sensory Neurons ◽  
Cranial Neural Crest ◽  
Loss Of Function

The sense of smell in vertebrates is detected by specialized sensory neurons derived from the peripheral nervous system. Classically, it has been presumed that the olfactory placode forms all olfactory sensory neurons. In contrast, we show that the cranial neural crest is the primary source of microvillous sensory neurons within the olfactory epithelium of zebrafish embryos. Using photoconversion-based fate mapping and live cell tracking coupled with laser ablation, we followed neural crest precursors as they migrated from the neural tube to the nasal cavity. A subset that coexpressed Sox10 protein and a neurogenin1 reporter ingressed into the olfactory epithelium and differentiated into microvillous sensory neurons. Timed loss-of-function analysis revealed a critical role for Sox10 in microvillous neurogenesis. Taken together, these findings directly demonstrate a heretofore unknown contribution of the cranial neural crest to olfactory sensory neurons in zebrafish and provide important insights into the assembly of the nascent olfactory system.

scholarly journals Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells

2011 ◽  
Vol 106 (3) ◽  
pp. 1274-1287 ◽  
Author(s):  
Tatsuya Ogura ◽  
Steven A. Szebenyi ◽  
Kurt Krosnowski ◽  
Aaron Sathyanesan ◽  
Jacqueline Jackson ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Transient Receptor Potential ◽  
Olfactory Sensory Neurons ◽  
Dependent Manner ◽  
Basal Cells ◽  
Supporting Cells ◽  
Concentration Dependent Manner ◽  
External Stimulation ◽  
Main Olfactory Epithelium

The mammalian olfactory epithelium is made up of ciliated olfactory sensory neurons (OSNs), supporting cells, basal cells, and microvillous cells. Previously, we reported that a population of nonneuronal microvillous cells expresses transient receptor potential channel M5 (TRPM5). Using transgenic mice and immunocytochemical labeling, we identify that these cells are cholinergic, expressing the signature markers of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter. This result suggests that acetylcholine (ACh) can be synthesized and released locally to modulate activities of neighboring supporting cells and OSNs. In Ca2+ imaging experiments, ACh induced increases in intracellular Ca2+ levels in 78% of isolated supporting cells tested in a concentration-dependent manner. Atropine, a muscarinic ACh receptor (mAChR) antagonist suppressed the ACh responses. In contrast, ACh did not induce or potentiate Ca2+ increases in OSNs. Instead ACh suppressed the Ca2+ increases induced by the adenylyl cyclase activator forskolin in some OSNs. Supporting these results, we found differential expression of mAChR subtypes in supporting cells and OSNs using subtype-specific antibodies against M1 through M5 mAChRs. Furthermore, we found that various chemicals, bacterial lysate, and cold saline induced Ca2+ increases in TRPM5/ChAT-expressing microvillous cells. Taken together, our data suggest that TRPM5/ChAT-expressing microvillous cells react to certain chemical or thermal stimuli and release ACh to modulate activities of neighboring supporting cells and OSNs via mAChRs. Our studies reveal an intrinsic and potentially potent mechanism linking external stimulation to cholinergic modulation of activities in the olfactory epithelium.

scholarly journals Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
B. Dnate’ Baxter ◽  
Eric D. Larson ◽  
Laetitia Merle ◽  
Paul Feinstein ◽  
Arianna Gentile Polese ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Infection ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Transient Receptor Potential ◽  
Transcriptional Profiling ◽  
Receptor Potential ◽  
Olfactory Nerve ◽  
Olfactory Sensory Neurons ◽  
Brush Cells

Abstract Background Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. Results Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons. Conclusion Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.

scholarly journals Centrioles are amplified via rosette formation in cycling progenitors of olfactory sensory neurons

2019 ◽  
Author(s):  
Kaitlin Ching ◽  
Tim Stearns
Keyword(s):  
Stem Cells ◽  
Embryonic Development ◽  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Rosette Formation ◽  
Olfactory Sensory Neurons ◽  
Centriole Duplication ◽  
Neuronal Precursors ◽  
Neuron Regeneration

AbstractOlfaction in most animals is mediated by neurons bearing cilia that are accessible to the environment. Olfactory sensory neurons (OSNs) in chordates usually have multiple cilia, each with a centriole at its base. OSNs differentiate from stem cells in the olfactory epithelium, and how the epithelium generates cells with many centrioles—about 16 in mouse—is not yet understood. We show that centrioles are amplified via centriole rosette formation in both embryonic development and turnover of the olfactory epithelium in adults, and rosette-bearing cells often have free centrioles in addition. Cells with amplified centrioles can go on to divide, with centrioles clustered at each pole. Additionally, we found that immediate neuronal precursors amplify centrioles concomitantly with elevation of mRNA for Plk4 and Stil, key regulators of centriole duplication. Our findings highlight the importance of accounting for centriole amplification in neuron regeneration therapies derived from olfactory epithelia.

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