Unique Synthetic Strategy for Probing in Situ Lysosomal NO for Screening Neuroinflammatory Phenotypes against SARS-CoV-2 RNA in Phagocytotic Microglia DOI
Subrata Munan, Abir Mondal,

Singh Shailja

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(19), P. 7479 - 7486

Published: May 1, 2024

In the pathogenesis of microglia, brain immune cells promote nitrergic stress by overproducing nitric oxide (NO), leading to neuroinflammation. Furthermore, NO has been linked COVID-19 progression, which caused significant morbidity and mortality. SARS-CoV-2 infection activates inflammation releasing excess causing cell death in human microglial clone 3 (HMC3). addition, regulates lysosomal functions complex machinery neutralize pathogens through phagocytosis. Therefore, developing lysosome-specific probes monitor phagocytosis microglia during would be a study. Herein, unique synthetic strategy was adopted develop selective fluorescent probe, PDM-NO, can discriminate activated from their resting state. The nonfluorescent PDM-NO exhibits turn-on response toward only at pH (4.5–5.5). Quantum chemical calculations (DFT/TD-DFT/PCM) photophysical study revealed that photoinduced electron transfer (PET) process is pivotal tuning optical properties. demonstrated good biocompatibility specificity HMC3 cells. Moreover, it effectively map dynamics against RNA-induced neuroinflammation HMC3. Thus, potential marker for detecting RNA virus monitoring

Language: Английский

Mechanisms of long COVID: An updated review DOI Creative Commons
Yan Liu, Xiaoying Gu, Haibo Li

et al.

Chinese Medical Journal - Pulmonary and Critical Care Medicine, Journal Year: 2023, Volume and Issue: 1(4), P. 231 - 240

Published: Dec. 1, 2023

The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than 3 years, with an enormous impact on global health and economies. In some patients, symptoms signs may remain after recovery from severe acute respiratory syndrome 2 (SARS-CoV-2) infection, which cannot be explained by alternate diagnosis; this condition defined as long COVID. Long COVID exist in patients both mild is prevalent infection different SARS-CoV-2 variants. most common include fatigue, dyspnea, other involving multiple organs. Vaccination results lower rates of To date, the mechanisms unclear. narrative review, we summarized clinical presentations current evidence regarding pathogenesis

Language: Английский

Citations

20
Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection DOI Creative Commons
Chang‐Yong Choi, Kundlik Gadhave,

Jason Villano

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(1)

Published: Jan. 1, 2024

Abstract Although the COVID‐19 pandemic has officially ended, persistent challenge of long‐COVID or post‐acute COVID sequelae (PASC) continues to impact societies globally, highlighting urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly long‐COVID/PASC research. This exhibits human expression in tissue cell‐specific patterns akin Ace2. When we exposed young adult hACE2ki mice (6 weeks old) various SARS‐CoV‐2 lineages, including WA, Delta, Omicron, at dose 5 × 10 PFU/mouse via nasal instillation, demonstrated distinctive phenotypes characterized by differences viral load lung, trachea, turbinate, weight loss, changes pro‐inflammatory cytokines immune cell profiles bronchoalveolar lavage fluid. Notably, no mortality was observed this age group. Further, assess model's relevance studies, investigated tau protein pathologies, which are linked Alzheimer's disease, brains these post infection. findings revealed accumulation longitudinal propagation tau, confirming potential our preclinical studies long‐COVID.

Language: Английский

Citations

8
Sex-specific biphasic alpha-synuclein response and alterations of interneurons in a COVID-19 hamster model DOI Creative Commons

Cara Sophie Schreiber,

Ivo Wiesweg,

Stephanie Stanelle-Bertram

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 105, P. 105191 - 105191

Published: June 13, 2024

Coronavirus disease 2019 (COVID-19) frequently leads to neurological complications after recovery from acute infection, with higher prevalence in women. However, mechanisms by which SARS-CoV-2 disrupts brain function remain unclear and treatment strategies are lacking. We previously demonstrated neuroinflammation the olfactory bulb of intranasally infected hamsters, followed alpha-synuclein tau accumulation cortex, thus mirroring pathogenesis neurodegenerative diseases such as Parkinson's or Alzheimer's disease.

Language: Английский

Citations

8
Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells DOI Creative Commons
Fiona Limanaqi, Silvia Zecchini, Irma Saulle

et al.

Biological Research, Journal Year: 2024, Volume and Issue: 57(1)

Published: Jan. 9, 2024

Abstract Background Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by variety viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute cell toxicity and the development and/or exacerbation neuropathological manifestations, it also key sustaining anti-viral innate immunity. Consistently with aggregation as hallmark Parkinson's disease, most studies investigating biological function focused on neural cells, while reports in periphery are limited, especially SARS-CoV-2 infection. Results herein obtained real time qPCR, immunofluorescence western blot indicate that upregulation peripheral cells occurs Type-I Interferon (IFN)-related response against Noteworthy, this effect mostly involves multimers, dynamic multimer:monomer ratio. Administration excess monomers promoted replication along downregulation IFN-Stimulated Genes (ISGs) epithelial lung which was associated reduced multimers These effects were prevented combined administration IFN-β, hindered virus upregulated ISGs, meanwhile increasing both ratio absence toxicity. Finally, endothelial displaying abortive replication, not exposure exogenous α-syn, suggesting only productive viral impairs multimerization equilibrium. Conclusions Our study provides novel insights into biology showing its conformations implicated immune cells. In particular, our results suggest promotion non-toxic likely IFN-related partakes suppression replication. Further needed replicate findings neuronal well animal models, ascertain nature such conformations.

Language: Английский

Citations

7
Mechanisms of COVID‐19‐associated olfactory dysfunction DOI
Koping Chang, Thomas D. Zaikos,

Nicholas Kilner‐Pontone

et al.

Neuropathology and Applied Neurobiology, Journal Year: 2024, Volume and Issue: 50(2)

Published: Feb. 28, 2024

Olfactory dysfunction is one of the most common symptoms COVID-19. In first 2 years pandemic, it was frequently reported, although its incidence has significantly decreased with emergence Omicron variant, which since become dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory an ongoing health concern. The proposed pathogenic mechanisms are complex likely multifactorial. While evidence suggests that infection sustentacular cells associated mucosal inflammation may be culprit acute, transient smell loss, alterations in other components system (e.g., receptor neuron dysfunction, bulb injury cortex) lead persistent, long-term dysfunction. This review aims provide a comprehensive summary epidemiology, clinical manifestations current understanding

Language: Английский

Citations

7
Potential convergence of olfactory dysfunction in Parkinson’s disease and COVID-19: The role of neuroinflammation DOI
Hui Li, Junliang Qian, Youcui Wang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102288 - 102288

Published: April 4, 2024

Language: Английский

Citations

7
Effects of nasal inflammation on the olfactory bulb DOI Creative Commons
Brandon J. LaFever, Fumiaki Imamura

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Dec. 9, 2022

Abstract Sinonasal diseases, such as rhinosinusitis, affect up to 12% of individuals each year which constitutes these diseases some the most common medical conditions in world. Exposure environmental pathogens and toxicants via nasal cavity can result a severe inflammatory state commonly observed conditions. It is well understood that epithelial neuronal cells lining olfactory mucosa, including sensory neurons (OSNs), are significantly damaged diseases. Prolonged inflammation may also lead hyposmia or anosmia. Although various agents induce different ways distinct cellular molecular interactions, has similar consequences on structure homeostatic function bulb (OB) first relay center for information brain. Atrophy OB occurs thinning superficial layers nerve layer, glomerular external plexiform layer. Intrabulbar circuits include connectivity between projection neurons, OSNs, interneurons become dysregulated synaptic pruning dendritic retraction take place. Furthermore, glial other immune hyperactivated results upregulated cytokine production. Moreover, many features present case SARS-CoV-2 infection. This review summarizes impact morphological physiological rodent OB.

Language: Английский

Citations

27
Mouse Adapted SARS-CoV-2 (MA10) Viral Infection Induces Neuroinflammation in Standard Laboratory Mice DOI Creative Commons

Narayanappa Amruta,

Saifudeen Ismael, Sarah R. Leist

et al.

Viruses, Journal Year: 2022, Volume and Issue: 15(1), P. 114 - 114

Published: Dec. 30, 2022

Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacts neurological function both acutely and chronically, even in the absence of pronounced distress. Developing clinically relevant laboratory mouse models neuropathogenesis SARS-CoV-2 is an important step toward elucidating underlying mechanisms SARS-CoV-2-induced dysfunction. Although various transgenic viral delivery methods have been used to study potential mice, use commonly available mice would facilitate neuropathology. Herein we show neuroinflammatory profiles immunologically intact C57BL/6J BALB/c, as well immunodeficient (Rag2-/-) a mouse-adapted strain coronavirus-2 (SARS-CoV-2 (MA10)). Our findings indicate brain IL-6 levels are significantly higher BALB/c male infected with MA10. Additionally, blood-brain barrier integrity, measured by vascular tight junction protein claudin-5, was reduced MA10 all three strains. Brain glial fibrillary acidic (GFAP) mRNA also elevated compared mock group. Lastly, immune-vascular effects (MA10), H&E scores, demonstrate increase perivascular lymphocyte cuffing (PLC) at 30 days post-infection among female significant PLC over time only MA10) mice. first (MA10) induces neuroinflammation could be novel model SARS-CoV-2-mediated cerebrovascular pathology.

Language: Английский

Citations

23
SARS‐CoV‐2 ORF3a expression in brain disrupts the autophagy–lysosomal pathway, impairs sphingolipid homeostasis, and drives neuropathogenesis DOI Creative Commons
Hongling Zhu,

Colleen Byrnes,

Y Terry Lee

et al.

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(5)

Published: April 18, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes injury to multiple organ systems, including the brain. SARS‐CoV‐2's neuropathological mechanisms may include systemic inflammation and hypoxia, as well direct cell damage resulting from viral infections of neurons glia. How virus directly brain cells, acutely over long term, is not understood. In order gain insight into this process, we studied effects open reading frame 3a (ORF3a), a SARS‐CoV‐2 accessory protein that key pathological factor virus. Forced ORF3a expression in mice caused rapid onset neurological impairment, neurodegeneration, neuroinflammation—key features found disease (COVID‐19, which by infection). Furthermore, blocked autophagy progression neuronal accumulation α‐synuclein glycosphingolipids, all are linked neurodegenerative disease. Studies with ORF3‐expressing HeLa cells confirmed disrupted autophagy–lysosomal pathway glycosphingolipid degradation, their accumulation. These findings indicate that, event neuroinvasion SARS‐CoV‐2, drive neuropathogenesis be an important mediator both short‐ long‐term manifestations COVID‐19.

Language: Английский

Citations

14
Microglial Inflammatory Responses to SARS‐CoV‐2 Infection: A Comprehensive Review DOI
Rajen Dey, Biswadev Bishayi

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 44(1)

Published: Dec. 15, 2023

Language: Английский

Citations

14