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Blood genome expression Profiles in Infants with Congenital Cytomegalovirus Infection: Is the asymptomatic infant truly asymptomatic?

ABSTRACT: Background: Congenital cytomegalovirus (cCMV) infection represents the most frequent non-genetic cause of sensorineural hearing loss (SNHL). The disease spectrum varies from clinically apparent (“symptomatic”) to clinically inapparent (“asymptomatic”). Analysis of host genome expression profiles has provided new insights into disease pathogenesis and assessment of clinical severity. Its value as a biomarker in infants with cCMV has not been explored. Methods: Infants with cCMV infection, both symptomatic and asymptomatic, were enrolled at a median age of 17 days of age and followed up for 3 years to assess the development of SNHL. Healthy age matched controls were also enrolled as a reference. Blood samples were obtained at enrollment and follow-up to assess host responses by RNA transcriptional profiling. Symptomatic CMV was defined as the presence of any clinical, laboratory, ophthalmologic, audiologic or neuroimaging abnormalities.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108211 | GEO | 2020/05/26

REPOSITORIES: GEO

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Project description:Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. All animal studies were carried out under approved IACUC protocols at the University of Washington.

Dataset Information

Blood genome expression Profiles in Infants with Congenital Cytomegalovirus Infection: Is the asymptomatic infant truly asymptomatic?

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