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Series GSE254984 Query DataSets for GSE254984
Status Public on Feb 23, 2024
Title Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary PASC (Post-Acute Sequelae of COVID-19) involves many organs, including most prominently the central nervous system. Most studies of PASC in laboratory animals were performed in the context of mild disease, but higher PASC prevalence is observed in patients with severe disease. Here, to investigate the basis of chronic neurological disease, we infected mice with mouse-adapted SARS-CoV-2 that causes severe respiratory disease but does not infect the brain. We assessed long-term effects on olfactory and substantia nigra (SN) function. While anosmia resolved within a few days, we observed long term loss of tyrosine hydroxylase (TH) expression in the olfactory bulb glomeruli, indicating chronically altered function of olfactory sensory neurons. These changes were accompanied by increased inflammation suggesting the involvement of the host immune response in anosmia-related changes. We also observed decreased neurotransmitter expression in the substantia nigra (SN) accompanied by increased levels of proinflammatory cytokines and neurobehavioral changes. Microglia have been implicated in long term changes in SARS-CoV-2 infected mice and in human neurodegenerative disease. RNAseq analysis of mouse brain microglia isolated several months after infection demonstrated key roles for these cells in ongoing pathogenesis. Finally, we showed that early treatment with antivirals (nirmatrelvir and molnupiravir) reduced virus titer and inflammation in the lung but did not prevent neurological abnormalities. Together these results show that these mice will be useful for probing the role of SARS-CoV-2 in the development of neurodegenerative disease, an aspect of disease not amenable to study in patients and that neurological PASC is not ameliorated by anti-viral therapy.
 
Overall design Comparative gene analysis between Mock and 100dpi mouse brain CD11b+ cells
 
Contributor(s) Verma AK, Perlman S, Abrahante Lloréns JE
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Submission date Feb 03, 2024
Last update date Feb 23, 2024
Contact name Abhishek K Verma
E-mail(s) abhishek-verma@uiowa.edu
Phone 6412305013
Organization name The University of Iowa
Department Department of Microbiology and Immunology
Lab Perlman Lab
Street address 3-730, Bowen Science Building, 51 Newton Road
City IOWA CITY
State/province IA
ZIP/Postal code 52242
Country USA
 
Platforms (1)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (8)
GSM8061733 Mock CD11b3
GSM8061734 Mock CD11b4
GSM8061735 Mock CD11b7
Relations
BioProject PRJNA1072976

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE254984_RawCounts_Pearlman006.csv.gz 742.3 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA

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