Transcriptomics

Dataset Information

8

Transcriptional profile of mice with good and poor spatial learning during West Nile virus recovery


ABSTRACT: Greater than 50% of patients who survive neuroinvasive West Nile virus (WNV), a mosquito-borne, positive-sense strand flavivirus, exhibit cognitive sequelae including memory impairments which may last several years. High survival rates from WNV neuroinvasive disease (WNND) (>90%) have led to hundreds to thousands of cases of WNV-mediated neurologic impairment accruing annually, yet underlying mechanisms responsible for these impairments have not been investigated. Here, we established a novel murine model of recovery from WNND in which intracranial inoculation of a mutant WNV (WNV-NS5-E218A) leads to rates of survival and cognitive dysfunction that mirror human WNND. WNV-NS5-E218A-recovered mice exhibit impaired spatial learning and persistently phagocytic microglia without significant loss of hippocampal neurons or brain volume. Whole transcriptome analysis of hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning was performed in order to identify target pathways and molecules underlying cognitive impairments during WNND recovery. Total RNA obtained from isolated murine hippocampus at 25 days post-mock or WNV-NS5-E218A intracranial infection.

ORGANISM(S): Mus musculus  

SUBMITTER: Robyn S Klein   Michael J Vasek  Jinsheng Yu 

PROVIDER: E-GEOD-72139 | ArrayExpress | 2016-06-27

SECONDARY ACCESSION(S): GSE72139PRJNA293167

REPOSITORIES: GEO, ArrayExpress

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Publications


Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Here we show that viral infection of adult hippocampal neurons induces complem  ...[more]

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