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Human-derived air–liquid interface cultures decipher Alzheimer’s disease–SARS-CoV-2 crosstalk in the olfactory mucosa
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SYSNO ASEP 0581035 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Human-derived air–liquid interface cultures decipher Alzheimer’s disease–SARS-CoV-2 crosstalk in the olfactory mucosa Tvůrce(i) Shahbaz, M. A. (FI)
Kuivanen, S. (FI)
Lampinen, R. (FI)
Mussalo, L. (FI)
Hron, Tomáš (UMG-J)
Závodná, Táňa (UEM-P)
Ojha, R. (FI)
Krejčík, Zdeněk (UEM-P)
Saveleva, L. (FI)
Tahir, N. A. (FI)
Kalapudas, J. (FI)
Koivisto, A. M. (FI)
Penttilä, E. (FI)
Löppönen, H. (FI)
Singh, P. (FI)
Topinka, Jan (UEM-P) RID, ORCID
Vapalahti, O. (FI)
Chew, S. (FI)
Balistreri, G. (US)
Kanninen, K. M. (FI)Celkový počet autorů 0 Číslo článku 299 Zdroj.dok. Journal of Neuroinflammation. - : Filtch Solutions
Roč. 20, č. 1 (2023)Poč.str. 23 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Air–liquid interface ; Alzheimer’s disease ; Anosmia ; covid-19 ; Immune responses ; Inflammation ; Neurological manifestations ; Olfactory ; SARS-CoV-2 Obor OECD Biochemistry and molecular biology CEP LM2018124 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF16_013/0001821 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Omezený přístup Institucionální podpora UEM-P - RVO:68378041 ; UMG-J - RVO:68378050 UT WOS 001125873300001 EID SCOPUS 85179765876 DOI 10.1186/s12974-023-02979-4 Anotace Background: The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD. Methods: To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air–liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing. Results: Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation. Conclusions: The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection. Graphical Abstract: [Figure not available: see fulltext.] Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2024 Elektronická adresa https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02979-4
Počet záznamů: 1