Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

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Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters

Clinical Infectious Diseases ◽

10.1093/cid/ciaa995 ◽

2020 ◽

Cited By ~ 11

Author(s):

Anna Jinxia Zhang ◽

Andrew Chak-Yiu Lee ◽

Hin Chu ◽

Jasper Fuk-Woo Chan ◽

Zhimeng Fan ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Olfactory Bulb ◽

Sensory Neurons ◽

Young Patients ◽

Olfactory Dysfunction ◽

Olfactory Sensory Neurons ◽

Specific Class ◽

Olfactory Neurons ◽

Viral Antigens ◽

Sustentacular Cells

Abstract Background Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain. Methods We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters. Results After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. Conclusions In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.

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The Impact of Oxidative Stress Factors on the Viability, Senescence, and Methylation Status of Olfactory Bulb-Derived Glial Cells Isolated from Human Cadaver Donors

Cells Tissues Organs ◽

10.1159/000472707 ◽

2017 ◽

Vol 204 (2) ◽

pp. 105-118

Author(s):

Krzysztof Marycz ◽

Katarzyna Kornicka ◽

Jakub Grzesiak ◽

Krzysztof A. Tomaszewski ◽

Dariusz Szarek ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Olfactory Bulb ◽

Glial Cells ◽

Methylation Status ◽

Stress Factors ◽

Molecular Characteristics ◽

Isolated Cells ◽

Promising Tool ◽

The Impact

The olfactory bulb (OB) is a unique structure in the central nervous system that retains the ability to create new neuronal connections. Glial cells isolated from the OB have been recently considered as a novel and promising tool to establish an effective therapy for central nervous system injuries. Due to the hindered access to autologous tissue for cell isolation, an allogeneic source of tissues obtained postmortem has been proposed. In this study, we focused on the morphological and molecular characteristics of human OB-derived glial cells isolated postmortem, at different time points after a donor's death. We evaluated the proliferative activity of the isolated cells, and investigated the ultrastructure of the mitochondria, the accumulation of intracellular reactive oxygen species, and the activity of superoxide dismutase. The data obtained clearly indicate that the duration of ischemia is crucial for the viability/senescence rate of OB-derived glial cells. The OB can be isolated during autopsy and still stand as a source of viable glial cells, but ischemia duration is a major factor limiting its potential usefulness in therapies.

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

10.21203/rs.3.rs-53345/v1 ◽

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.

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Map-independent representation of an aggression-promoting social cue in the main olfactory pathway

10.1101/2021.12.30.474554 ◽

2021 ◽

Author(s):

Annika Cichy ◽

Adam Dewan ◽

Jingji Zhang ◽

Sarah Kaye ◽

Tiffany Teng ◽

...

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Mammalian Species ◽

Olfactory Sensory Neurons ◽

Olfactory Pathway ◽

Male Aggression ◽

Transgenic Expression ◽

Mouse Urine ◽

State Dependent ◽

Specific Odor

While the olfactory system is required for proper social behaviors, the molecular basis for how social cues are detected via the main olfactory pathway of mammals is not well-characterized. Trimethylamine is a volatile, sex-specific odor found in adult male mouse urine that selectively activates main olfactory sensory neurons that express trace amine-associated receptor 5 (TAAR5). Here we show that trimethylamine, acting via TAAR5, elicits state-dependent attraction or aversion in male mice and drives inter-male aggression. Genetic knockout of TAAR5 significantly reduces aggression-related behaviors, while adding trimethylamine augments aggressive behavior towards juvenile males. We further show that transgenic expression of TAAR5 specifically in olfactory sensory neurons rescues aggressive behaviors in knockout mice, despite extensive remapping of TAAR5 projections to the olfactory bulb. Our results identify a specific main olfactory input that detects a prominent male-specific odor to induce inter-male aggression in a mammalian species and reveal that apparently innate behavioral responses are independent of patterned glomerular input to the olfactory bulb.

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Effect of Homocysteine on Survival of Human Glial Cells

Physiological Research ◽

10.33549/physiolres.932897 ◽

2015 ◽

pp. 747-754 ◽

Cited By ~ 15

Author(s):

H. ŠKOVIEROVÁ ◽

S. MAHMOOD ◽

E. BLAHOVCOVÁ ◽

J. HATOK ◽

J. LEHOTSKÝ ◽

...

Keyword(s):

Adverse Effect ◽

Cell Death ◽

Cognitive Impairment ◽

Glial Cells ◽

Culture Medium ◽

Glioblastoma Cell Line ◽

Glioblastoma Cell ◽

Mild Hyperhomocysteinemia ◽

Neuronal Functions ◽

The Impact

Several neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease, or vascular dementia and cognitive impairment, are associated with mild hyperhomocysteinemia. Hyperhomocysteinemia is defined as an increase of the homocysteine (Hcy) level beyond 10 μM. Although the adverse effect of Hcy on neurons is well documented, knowledge about the impact of this amino acid on glial cells is missing. Therefore, with the aim to evaluate the neurotoxic properties of Hcy on glial cells, we used a glioblastoma cell line as a study model. The viability of cells was assayed biochemically and cytologically. At a concentration around 50 μM in the culture medium D,L-Hcy induced cell death. It is noteworthy that Hcy induces cell death of human glial cells at concentrations encountered during mild hyperhomocysteinemia. Therefore, we propose that Hcy-induced impairment of neuronal functions along with damage of glial cells may contribute to the etiopathogenesis of neurodegenerative diseases associated with hyperhomocysteinemia.

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Study of the glial cytoarchitecture of the developing olfactory bulb of a shark using immunochemical markers of radial glia

Brain Structure and Function ◽

10.1007/s00429-021-02448-9 ◽

2022 ◽

Author(s):

A. Docampo-Seara ◽

E. Candal ◽

M. A. Rodríguez

Keyword(s):

Olfactory Bulb ◽

Glial Cells ◽

Radial Glia ◽

Developmental Stages ◽

Olfactory Nerve ◽

Lipid Binding ◽

Ependymal Cells ◽

Olfactory Pathway ◽

Radial Glial Cells ◽

Central Origin

AbstractDuring development of the olfactory bulb (OB), glial cells play key roles in axonal guiding/targeting, glomerular formation and synaptic plasticity. Studies in mammals have shown that radial glial cells and peripheral olfactory glia (olfactory ensheathing cells, OECs) are involved in the development of the OB. Most studies about the OB glia were carried out in mammals, but data are lacking in most non-mammalian vertebrates. In the present work, we studied the development of the OB glial system in the cartilaginous fish Scyliorhinus canicula (catshark) using antibodies against glial markers, such as glial fibrillary acidic protein (GFAP), brain lipid-binding protein (BLBP), and glutamine synthase (GS). These glial markers were expressed in cells with radial morphology lining the OB ventricle of embryos and this expression continues in ependymal cells (tanycytes) in early juveniles. Astrocyte-like cells were also observed in the granular layer and surrounding glomeruli. Numerous GS-positive cells were present in the primary olfactory pathway of embryos. In the developmental stages analysed, the olfactory nerve layer and the glomerular layer were the regions with higher GFAP, BLBP and GS immuno-reactivity. In addition, numerous BLBP-expressing cells (a marker of mammalian OECs) showing proliferative activity were present in the olfactory nerve layer. Our findings suggest that glial cells of peripheral and central origin coexist in the OB of catshark embryos and early juveniles. These results open the path for future studies about the differential roles of glial cells in the catshark OB during embryonic development and in adulthood.

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