scholarly journals Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb

2021 ◽  
pp. 1-10
Author(s):  
Moritz Klingenstein ◽  
Stefanie Klingenstein ◽  
Peter H. Neckel ◽  
Andreas F. Mack ◽  
Andreas P. Wagner ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Respiratory Epithelium ◽  
Olfactory Receptor Neurons ◽  
Basal Cells ◽  
Sustentacular Cells ◽  
Glandular Cells ◽  
Receptor Neurons ◽  
Human Nose

Usually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough, but frequently also with anosmia and neurological symptoms. Virus-cell fusion is mediated by angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to the central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human postmortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium as well as in the respiratory epithelium of the nasal septum, the nasal conchae, and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium as well as in the basal cells, glandular cells, and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly, ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium. Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium, and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia via the olfactory pathway.

scholarly journals Evidence of SARS-CoV2 entry protein ACE2 in the human nose and olfactory bulb

2020 ◽  
Author(s):  
M. Klingenstein ◽  
S. Klingenstein ◽  
P.H. Neckel ◽  
A. F. Mack ◽  
A. Wagner ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Respiratory Epithelium ◽  
Olfactory Receptor Neurons ◽  
Basal Cells ◽  
Sustentacular Cells ◽  
Glandular Cells ◽  
Receptor Neurons ◽  
Human Nose

ABSTRACTUsually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough but frequently also with anosmia and neurological symptom. Virus-cell fusion is mediated by Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human, post-mortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium, as well as in the respiratory epithelium of the nasal septum, the nasal conchae and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium, as well as in the basal cells, glandular cells and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium.Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia of via the olfactory pathway.

Physiological activity of newly differentiated olfactory receptor neurons correlated with morphological recovery from olfactory nerve section in the salamander

1981 ◽  
Vol 45 (3) ◽  
pp. 529-549 ◽  
Author(s):  
P. A. Simmons ◽  
T. V. Getchell
Keyword(s):  
Olfactory Bulb ◽  
Spontaneous Activity ◽  
Histological Examination ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Receptor Cell ◽  
Olfactory Nerve ◽  
Olfactory Receptor Neurons ◽  
Nerve Section ◽  
Receptor Neurons

1. Extracellular unitary recordings were made from the olfactory epithelium of the salamander, Ambystoma tigrinum, at numerous time points following olfactory nerve section. Unitary response properties were correlated with histological examination of the same tissues. 2. At 10 days following nerve section, unitary activity was rarely recorded in all regions of the epithelium. Histological examination indicated that virtually the entire mature olfactory receptor cell population had undergone retrograde degeneration. Transneuronal degeneration was not observed in the olfactory bulb, although the olfactory nerve and glomerular layers were substantially reduced in size. 3. At subsequent times, unitary impulse activity gradually returned, consisting of both spontaneous activity and odor-evoked discharges. Anatomical recovery of the olfactory epithelium preceded that of the olfactory bulb. A positive correlation was found between neuronal differentiation in the olfactory epithelium and the recovery of receptor cell function. 4. Patterns of spontaneous activity, odor specificities, intensity-response functions, and adaptive properties studied in newly differentiated olfactory receptor neurons were indistinguishable from those observed in control units. This indicated that these properties were intrinsic to the receptor neurons. 5. Spontaneously active and responsive units were encountered prior to olfactory nerve connection with the bulb. It is concluded that receptor neurons pass through two phases of functional maturity: the first independent of bulbar contact and the second dependent on presumed synaptic contact with bulbar neurons.

Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

2007 ◽  
Vol 293 (2) ◽  
pp. C574-C583 ◽  
Author(s):  
Barbara R. Grubb ◽  
Troy D. Rogers ◽  
Heather M. Kulaga ◽  
Kimberlie A. Burns ◽  
Robert L. Wonsetler ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Ussing Chamber ◽  
Fold Increase ◽  
Olfactory Receptor Neurons ◽  
Sodium Absorption ◽  
Sustentacular Cells ◽  
Sensory Cilia ◽  
Morphological Defects ◽  
Receptor Neurons ◽  
Chamber Studies

In normal nasal epithelium, the olfactory receptor neurons (ORNs) are continuously replaced through the differentiation of progenitor cells. The olfactory epithelium (OE) of the cystic fibrosis (CF) mouse appears normal at birth, yet by 6 mo of age, a marked dysmorphology of sustentacular cells and a dramatic reduction in olfactory receptor neurons are evident. Electroolfactograms revealed that the odor-evoked response in 30-day-old CF mice was reduced ∼45%; in older CF mice, a ∼70% reduction was observed compared with the wild type (WT) response. Consistent with studies of CF airway epithelia, Ussing chamber studies of OE isolated from CF mice showed a lack of forskolin-stimulated Cl− secretion and an ∼12-fold increase in amiloride-sensitive sodium absorption compared with WT mice. We hypothesize that the marked hyperabsorption of Na+, most likely by olfactory sustentacular cells, leads to desiccation of the surface layer in which the sensory cilia reside, followed by degeneration of the ORNs. The CF mouse thus provides a novel model to examine the mechanisms of disease-associated loss of olfactory function.

Neuronal nitric oxide synthase-like immunoreactivity in olfactory epithelium throughout the life cycle of the sea lamprey, Petromyzon marinus L.

2000 ◽  
Vol 78 (3) ◽  
pp. 346-351 ◽  
Author(s):  
Hong N Hua ◽  
Aliya U Zaidi ◽  
Barbara S Zielinski
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Petromyzon Marinus ◽  
Neuronal Nitric Oxide Synthase ◽  
Sea Lamprey ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons ◽  
Oxide Synthase

This study is the first to show that neuronal nitric oxide synthase-like immunoreactivity is located in the olfactory epithelium at all developmental stages of a vertebrate. Western immunoblotting of sea lamprey (Petromyzon marinus L.) olfactory mucosa with a monoclonal antibody against the NADPH-binding epitope of neuronal nitric oxide synthase showed that the molecular mass of this protein was 200 kDa. In the larval stage, neuronal nitric oxide synthase-like immunoreactivity was strongest in the basal region of the olfactory epithelium, the site of proliferating olfactory receptor neurons. This staining gradually diminished as the life cycle progressed. In the juvenile stage, the intensity of neuronal nitric oxide synthase-like immunoreactivity was striking in the wide cell bodies and dendrites on olfactory receptor neurons. These results confirm previous evidence that nitric oxide modulates development in the olfactory epithelium.

scholarly journals Accumulation of stress-related proteins within the glomeruli of the rat olfactory bulb following damage to olfactory receptor neurons

2008 ◽  
Vol 71 (4) ◽  
pp. 265-277 ◽  
Author(s):  
Kazuho Hirata ◽  
Takaaki Kanemaru ◽  
Motozumi Minohara ◽  
Akinobu Togo ◽  
Jun-ichi Kira
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Receptor ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons ◽  
Related Proteins

Neurogenesis in olfactory epithelium: loss and recovery of transepithelial voltage transients following olfactory nerve section

1981 ◽  
Vol 45 (3) ◽  
pp. 516-528 ◽  
Author(s):  
P. A. Simmons ◽  
T. V. Getchell
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Time Course ◽  
Olfactory Nerve ◽  
Nerve Section ◽  
Retrograde Degeneration ◽  
Transepithelial Voltage ◽  
Receptor Neurons ◽  
Voltage Transients

1. Unilateral olfactory nerve section was performed on the salamander, Ambystoma tigrinum. Physiological recordings and macroscopic observations were made to investigate the physiological correlates of functional recovery in the olfactory epithelium. 2. Slow transepithelial voltage transients, Veog, evoked by several odorous stimuli systematically decreased in amplitude during the initial 7 days and were not recorded at 10 days following nerve section, suggesting retrograde degeneration of receptor neurons. This was true for negative Veog(-), and positive, Veog(+), response components. Responses obtained from the untreated contralateral side of each animal remained similar to nonaxotomized controls. 3. Progressive recovery of the voltage transients was studied at 24, 45, 80, and 100 days following nerve section. At all stages of recovery, the wave form and time course of the responses were characteristic for each stimulus. This suggested that the response properties of the newly differentiated neuronal population were similar to those of the mature population. 4. At 100 days, response amplitudes evoked by all stimuli were similar to control values at all recording sites on the epithelial surface. The simultaneous loss and recovery of positive and negative components of the Veog indicated that the sources of both are dependent on the presence of functionally mature olfactory receptor neurons. 5. Visual inspection indicated that the olfactory nerve was reconstituted and reconnected to the olfactory bulb between 30-60 days following transection. The fact that physiological activity was recorded in the epithelium prior to this event suggests that molecular recognition and sensory transduction are not dependent on connectivity with the olfactory bulb. 6. It is concluded that physiological recovery of the olfactory receptor cell population occurs following axotomy. The time course of recovery was consistent with morphological evidence (see Ref. 57), indicating that newly differentiated receptor neurons are derived from cells in the basal region of the epithelium and replace the population lost through retrograde degeneration.

scholarly journals Comparison of the Nasal Olfactory Organs of Various Species of Lizardfishes (Teleostei: Aulopiformes: Synodontidae) with Additional Remarks on the Brain

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
L. Fishelson ◽  
D. Golani ◽  
B. Galil ◽  
M. Goren
Keyword(s):  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Olfactory Receptor Neurons ◽  
Adult Fish ◽  
Supporting Cells ◽  
Receptor Neurons ◽  
Olfactory Organs ◽  
Species Specific ◽  
The Brain

The olfactory organs of lizardfishes (Synodontidae) are situated in two capsules connected to the outside by incurrent and excurrent openings. The olfactory epithelium is in form of petal rosettes each composed of lamellae and a rephe, and bear olfactory receptor neurons, supporting cells and cells with kinocillia. The dimension of rosettes and lamellae, as well as the number of lamellae, increase with growth of the fish; until in adult fish these parameters remaine constant, species specific. In adultSynodusspp. andTrachinocephalus myopsthe rosettes are 3.5–4.0 mm long, with 5–8 lamellae, whereas inSauridaspp. they are 8.0 mm and possess up tp 22 lamellae. The number of ORN ranges from 2,600 on the smaller lamellae to 20,000 on the largest ones. The number of ORN/m of olfactory is ca. 30,000 inSauridaspp. Thus the rosettes ofS. macrolepiswith 20 lamellae possess a total of ca. 170,000 ORN, whereas those ofSy. variegatusandT. myopswith the average of six lamellae possess only ca. 50,000–65,000 ORN. The olfactory nerves lead from the rosettes to the olfactory balbs situated on the olfactory lobes. The differences among the species in olfactory organs are discussed in correlation with their distribution.

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