Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 12, 2023

ABSTRACT Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS CoV-2 induced neuropathology remains largely unclear. Since the choroid plexus (CP) performs important barrier and immune-interface functions, secretes cerebrospinal fluid strongly expresses ACE2 receptor chromosome 21 encoded TMPRSS2 protease, we hypothesized that CP could play a role in establishing SARS-CoV-2 infection brain. To investigate of central nervous system DS, established new type brain organoid from DS isogenic euploid control iPSC consists core appropriately patterned functional cortical neuronal cell types is surrounded by patent (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features development but also revealed defects ciliogenesis epithelial polarity developing plexus. We next demonstrate layer facilitates replication cells, this increased DS-CPCOs. further show inhibition Furin activity inhibits CPCOs level observed organoids. conclude useful model for dissecting forebrain enables screening therapeutics can inhibit neuro-pathogenesis.

Language: Английский

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Does COVID-19 Trigger the Risk for the Development of Parkinson’s Disease? Therapeutic Potential of Vitamin C

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(12), P. 9945 - 9960

Published: Nov. 14, 2023

Language: Английский

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Sensory Dysfunction, Microbial Infections, and Host Responses in Alzheimer's Disease

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: 230(Supplement_2), P. S150 - S164

Published: June 27, 2024

Abstract Sensory functions of organs the head and neck allow humans to interact with environment establish social bonds. With aging, smell, taste, vision, hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy pathological including development Alzheimer's disease (AD) other neurological disorders. While drivers early alteration AD are not elucidated, insults such as trauma infections affect function. Herein, we review involvement major systems AD, emphasis on microbes exploiting pathways enter brain (the “gateway” hypothesis) potential feedback loop by which function may be impacted central nervous system infection. We emphasize detection changes first-line surveillance senior adults identify remove insults, like microbial infections, could precipitate pathology.

Language: Английский

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Understanding Post-COVID-19: Mechanisms, Neurological Complications, Current Treatments, and Emerging Therapies

International Journal of General Medicine, Journal Year: 2024, Volume and Issue: Volume 17, P. 6303 - 6321

Published: Dec. 1, 2024

COVID-19, a highly infectious disease, caused worldwide pandemic in early 2020. According to the World Health Organization (WHO), COVID-19 has resulted approximately 774 million cases and around 7 deaths. The effects of are well known; however, there is lack information on pathophysiological mechanisms underlying symptoms that comprise Post-Acute Syndrome (PACS) or Long COVID-19. Neurological sequelae common, with cognitive dysfunction being one foremost symptoms. Research indicates elevated inflammatory levels increased oxidative stress may play role etiology severity PACS. Treatment options extremely limited, no consensus among medical scientific communities how manage disease. Nevertheless, many scientists advocate for using antioxidants symptomatic therapy behavior supportive care. Additionally, current research aims ameliorate several aspects cascade. This review highlights intracellular extracellular pathways crucial neurological manifestations PACS, providing valuable healthcare professionals scientists. Given complex nature understanding these essential developing new treatment options. Assessing PACS challenging, reviewing therapeutic while proposing triad potential elements will add value clinical assays guidelines. Current strategies, such as antioxidants/vitamin supplements, neurogenic stem cell therapy, mitochondrial could be combined enhance their effectiveness. Future should focus validating approaches exploring avenues effective

Language: Английский

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Identification of Natural Compounds for Long COVID Based on Hub Gene Biomarkers and Repurposed Drugs

Published: Aug. 13, 2024

Long COVID is a phenomenon in which individuals experience persistent symptoms after recovering from COVID-19. The are discovered to be unique for every individual and can affect multiple organs systems the body. This study aims identify effective natural remedies long by analyzing hub genes associated with of condition evaluating repurposed drugs catered used treating COVID. most common prevalent were identified; Fatigue, Shortness Breath, Loss Smell, Headache, Brain Fog, Chest Pain, Insomnia, Heart Palpitations, Dizziness, Joint Depression, Anxiety, Tinnitus, Appetite. Hub each provided an insight on key biological pathways symptom. Repurposed identified, template compounds similar structure as potential therapeutic drug. retrieved using fingerprint search NPASS Database. findings this suggest several symptom based molecular docking gene compound iGEMDOCK. identified may hold promise COVID, but further research required explore efficacy effectiveness proposed compounds. results pose important implications development treatments

Language: Английский

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Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study

International Journal of Environmental Research and Public Health, Journal Year: 2023, Volume and Issue: 20(17), P. 6678 - 6678

Published: Aug. 29, 2023

(1) Background: A substantial proportion of COVID-19 patients continue to experience long-lasting effects that hamper their quality life. The objectives this study were report the prevalence persistent clinical symptoms 6–12 months after onset and (2) identify potential factors at admission associated with occurrence long COVID. Methods: prospective was conducted among adult patients, hospitalized in four French university hospitals. Patients invited two ambulatory follow-up medical visits, 6–8 (visit #1) one year #2) COVID-19. multivariate logistic regression performed assess (3) Results: In total, 189 participated (mean age 63.4 years). BMI > 30 kg/m2 (aOR 3.52), AST levels between 31 42 U/L 8.68), 3.69) visit #1. Anosmia 13.34), 10.27), stay ICU 5.43), pain 4.31), longer time before hospitalization 1.14) significantly #2. ageusia 0.17) had a lower risk (4) Conclusions: This showed some experienced determinants acute phase/stage.

Language: Английский

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Deprivation-induced plasticity in the early central circuits of the rodent visual, auditory, and olfactory systems

eNeuro, Journal Year: 2024, Volume and Issue: unknown, P. ENEURO.0435 - 23.2023

Published: Jan. 9, 2024

Activity-dependent neuronal plasticity is crucial for animals to adapt dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily cortices. Nevertheless, emerging evidence emphasizes its significance organs and sub-cortical regions where cranial nerves relay information the brain. Additionally, critical questions started arise. Do different modalities share common cellular mechanisms deprivation-induced at these central entry-points? Does duration correlate with specific mechanisms? This study systematically reviews meta-analyses research papers that visual, auditory, or olfactory rodents of both sexes. It examines consequences homologous first synapse following nerve transmission (vision-lateral geniculate nucleus superior colliculus; audition-ventral dorsal cochlear nucleus; olfaction-olfactory bulb). The systematic search yielded 91 (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity publication trends, experimental methods, measures plasticity, reporting across modalities. Despite differences, commonalities emerged when correlating deprivation. Short-term (up 1 day) reduced activity increased disinhibition, medium-term (1 day a week) involved glial changes synaptic remodelling, long-term (over led structural alterations. These findings underscore importance standardizing methodologies practices. they highlight value cross-modals synthesis understanding how nervous system, including peripheral, pre-cortical, cortical areas, respond compensate inputs loss. Significance Statement addresses issue loss impact on brain's adaptability, shedding light systems from environment. While past explored early-life deprivation, this focuses effects post-weaning rodents. By reviewing articles, reveal distinct responses based not only enhances our brain but also broad implications translational applications, particularly cross-modal offering valuable insights into neuroscientific potential clinical interventions.

Language: Английский

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The long-term effect of COVID-19 infection on olfaction and taste; a prospective analysis

European Archives of Oto-Rhino-Laryngology, Journal Year: 2024, Volume and Issue: 281(11), P. 6001 - 6007

Published: July 8, 2024

To estimate long-term prognosis of chemosensory dysfunctions among patients recovering from COVID-19 disease.

Language: Английский

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Persistence of Olfactory Dysfunction in Post CoVid-19 Patients Using Sniffin Sticks-A Prospective Study

Bengal Journal of Otolaryngology and Head Neck Surgery, Journal Year: 2024, Volume and Issue: 32(1), P. 37 - 42

Published: Nov. 29, 2024

INTRODUCTION This study is conducted to assess the Olfactory dysfunction (OD) of CoVid-19 recovered patients using ODOFIN Sniffin’ Sticks and analyze demographic features, duration recovery, co-morbidities/metabolic disorders associated with persistence OD in Post patients. MATERIALS AND METHODS Prospective observational was at our tertiary care hospital on 40 persistent OD. The olfaction assessed qualitatively sticks 6th, 10th, 12th weeks CoVid results documented analysed. RESULTS Total eligible were selected. 50% participants males 60% aged 18-38 years. 3 Diabetic Hypertensive. 37 had which 26 Hyposmia 11 Anosmia 6 CoVid. 22 14 8 10 12 There no association found between age, co-morbidities 6, (p>0.05). common among females be statistically significant (p<0.05). CONCLUSION Knowledge about time pattern recovery will essential counselling treating them.

Language: Английский

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An Epigenetic Locus Associated with Loss of Smell in COVID-19

Diagnostics, Journal Year: 2024, Volume and Issue: 14(24), P. 2823 - 2823

Published: Dec. 15, 2024

Background/Aim: Loss of smell, also known as anosmia, is a prevalent and often prolonged symptom following infection with SARS-CoV-2. While many patients regain olfactory function within weeks, significant portion experience persistent anosmia lasting over year post-infection. The underlying mechanisms responsible for this sensory deficit remain largely uncharacterized. Previous studies, including genome-wide association studies (GWAS), have identified genetic variants near the UGT2A1 UGT2A2 genes that are linked to in COVID-19 patients. However, role epigenetic changes development persistence smell loss has not been well explored. In study, we aimed investigate alterations form DNA methylation UGT1A1 gene, which locus associated dysfunction Methods: We analysed patterns blood samples from two carefully matched cohorts 20 each, differentiated by their function—those normal (normosmia) those suffering (anosmia). were age sex minimize potential confounding factors. Results: Using quantitative analysis, found significantly lower levels group compared normosmia group, 14% decrease median values (p < 0.0001). These findings highlight epigenomic gene may contribute pathogenesis infection. Our results suggest status at could serve biomarker affected individuals. Conclusion: This study among first describe COVID-19, providing foundation future research into targeted interventions therapeutic strategies reversing anosmia. Further investigations involving larger additional loci help elucidate complex interaction between genetic, epigenetic, environmental factors influencing long-term impairment post-COVID-19.

Language: Английский

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