Time and age-dependent pathway enrichment analysis of gene expression in immature and mature rats after kainate-induced status epilepticus
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Craige, Michael W..
Time and age-dependent pathway enrichment analysis of gene expression in immature and mature rats after kainate-induced status epilepticus. Retrieved from
https://doi.org/doi:10.7282/t3-vyzd-qm27
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TitleTime and age-dependent pathway enrichment analysis of gene expression in immature and mature rats after kainate-induced status epilepticus
Date Created2021
Other Date2021-08 (degree)
Extent1 online resource (xii, 131 pages) : illustrations
DescriptionEpilepsy is a severe and potentially life-threatening neurologic condition and is the most common brain disorder worldwide (Thurman et al., 2011), affecting approximately 1.2% of the global population. Yet, the molecular pathways involved in the development of epilepsy remain poorly understood. To address this problem, I analyzed gene expression profiles using mRNA isolated from the hippocampi of immature (P15) and mature (P30) rats following treatment with kainic acid (KA), a glutamate agonist with well-studied seizure-inducing activity. Samples were obtained at 5-time points following KA administration (1 hr., 6 hrs., 24 hrs., 72 hrs., and 240 hrs.) and applied to an Affymetrix gene chip (8799 genes). While both P15 and P30 animals experience status epilepticus (SE) in response to KA injection, only the P30 animals develop spontaneous recurrent seizures. Data were analyzed using the Gene Set Enrichment Analysis (GSEA) Java-based desktop application and four (4) C2 MSigDB biological pathways, coupled with original Python (v3.8.5) scripts, to identify key molecular pathways that were significantly altered in response to KA-induced SE in P15 and P30 animals.
We identified 132 differentially regulated pathways between the P15 and P30 animals, including pathways involved in oxidative phosphorylation, inflammation, cell activation, cell cycle transit, apoptosis, proteasome activity, and MHC I antigen presentation transcription and translation. Examination of individual gene expression within these pathways identified several differentially expressed neuronal stress response and survival genes, including MeCP-2, netrin-1 receptors, and AKT2, which merit further individual analysis, as they may potentially serve as therapeutic targets.
The development of specific computational tools and their application in pathway-centric analyses of events during epileptogenesis represents significant and valuable innovations. This approach allows a deeper mechanistic understanding of the biological processes governing epilepsy. The computational tools developed during this study provide an extensive resource to a broader scientific community to analyze complex biological events.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
LanguageEnglish
CollectionSchool of Health Professions ETD Collection
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.