دورية أكاديمية
أعرض في EDS

Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus.

التفاصيل البيبلوغرافية
العنوان: Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus.
المؤلفون: Lemcke R; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Egebjerg C; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Berendtsen NT; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Egerod KL; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Thomsen AR; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Pers TH; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Christensen JP; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Kornum BR; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
المصدر: ELife [Elife] 2023 Sep 12; Vol. 12. Date of Electronic Publication: 2023 Sep 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Influenza, Human* , Influenza A Virus, H1N1 Subtype*, Animals ; Mice ; Humans ; Hypothalamus ; Solitary Nucleus ; Appetite
مستخلص: Infection with Influenza A virus (IAV) causes the well-known symptoms of the flu, including fever, loss of appetite, and excessive sleepiness. These responses, mediated by the brain, will normally disappear once the virus is cleared from the system, but a severe respiratory virus infection may cause long-lasting neurological disturbances. These include encephalitis lethargica and narcolepsy. The mechanisms behind such long lasting changes are unknown. The hypothalamus is a central regulator of the homeostatic response during a viral challenge. To gain insight into the neuronal and non-neuronal molecular changes during an IAV infection, we intranasally infected mice with an H1N1 virus and extracted the brain at different time points. Using single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus, we identify transcriptional effects in all identified cell populations. The snRNA-seq data showed the most pronounced transcriptional response at 3 days past infection, with a strong downregulation of genes across all cell types. General immune processes were mainly impacted in microglia, the brain resident immune cells, where we found increased numbers of cells expressing pro-inflammatory gene networks. In addition, we found that most neuronal cell populations downregulated genes contributing to the energy homeostasis in mitochondria and protein translation in the cytosol, indicating potential reduced cellular and neuronal activity. This might be a preventive mechanism in neuronal cells to avoid intracellular viral replication and attack by phagocytosing cells. The change of microglia gene activity suggest that this is complemented by a shift in microglia activity to provide increased surveillance of their surroundings.
Competing Interests: RL, CE, NB, KE, AT, TP, JC, BK No competing interests declared
(© 2023, Lemcke et al.)
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فهرسة مساهمة: Keywords: hypothalamus; immunology; inflammation; influenza a virus; mouse; neurons; neuroscience; non-neuronal cells; olfactory bulb; snRNA sequencing; viruses
Local Abstract: [plain-language-summary] When you are ill, your behaviour changes. You sleep more, eat less and are less likely to go out and be active. This behavioural change is called the ‘sickness response’ and is believed to help the immune system fight infection. An area of the brain called the hypothalamus helps to regulate sleep and appetite. Previous research has shown that when humans are ill, the immune system sends signals to the hypothalamus, likely initiating the sickness response. However, it was not clear which brain cells in the hypothalamus are involved in the response and how long after infection the brain returns to its normal state. To better understand the sickness response, Lemcke et al. infected mice with influenza then extracted and analysed brain tissue at different timepoints. The experiments showed that the major changes to gene expression in the hypothalamus early during an influenza infection are not happening in neurons – the cells in the brain that transmit electrical signals and usually control behaviour. Instead, it is cells called glia – which provide support and immune protection to the neurons – that change during infection. The findings suggest that these cells prepare to protect the neurons from influenza should the virus enter the brain. Lemcke et al. also found that the brain takes a long time to go back to normal after an influenza infection. In infected mice, molecular changes in brain cells could be detected even after the influenza infection had been cleared from the respiratory system. In the future, these findings may help to explain why some people take longer than others to fully recover from viral infections such as influenza and aid development of medications that speed up recovery.
سلسلة جزيئية: GEO GSE226098
تواريخ الأحداث: Date Created: 20230912 Date Completed: 20230913 Latest Revision: 20230925
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10497288
DOI: 10.7554/eLife.87515
PMID: 37698546
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.87515