481 Subacute Cell Specific Gene Expression Changes After Experimental TBI Suggest Target Genes for Cognitive Dysfunction. (1st April 2022)

• Record Type: Journal Article
• Authors: Alfawares, Yara; Correll, Erika; McGuire, Jennifer; Ngwenya, Laura B.
• Is Part Of: Neurosurgery. Volume 68(2022)Supplement 1
• Page Start: 119
• Page End: 119
• Publication Date: 2022-04-01
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1227/NEU.0000000000001880_481
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract : INTRODUCTION: Approximately 1.8 million Americans suffer from traumatic brain injury (TBI) each year, many of whom develop persistent cognitive difficulties. Understanding gene expression changes in cell types important for cognitive function may provide insight for therapeutic targets. METHODS: The dentate gyrus was dissected from the hippocampi of adult Sprague Dawley rats three weeks after either control or moderate lateral fluid percussion injury. Nuclei were isolated, the RNA was extracted, and sequenced using 10X Genomics technology. The RNA sequences were mapped to the rat genome (Rnor 6.0), quantified, and their expression normalized. Clustering of nuclei based on their gene expression profiles was done using Seurat (v4.0.1; R version 4.0.5). The granule cell cluster from each sample was identified based on expression of Prox1 and Rfx3, along with other neuronal markers. Genes with significant negatively correlated expressions between conditions were identified as differentially expressed and their functions were explored through Gene Ontology (GO). RESULTS: We identified a total of 14819 genes expressed in the granule cell clusters. Of these, 85 were differentially expressed. We identified twelve statistically significant biological processes using GO terms. GO terms with implications for cognitive function included: memory (p=0.000191, GO:0007613), negative regulation of amyloid-beta formation (p=0.000192, GO:1902430), and protein-lipid complex assembly (p=0.000192, GO:0065005). Statistically significant genes of interest associated with GO terms were under-expressed in the TBI condition: Apoe (p=0.00039), Atad1 (p=0.000013), Cpe (p=0.000438), and Dbn1 (0.002505). CONCLUSION: Three weeks after experimental TBI, hippocampal dentate granule cells under-express genes important for neurotransmitter receptor trafficking and neuronal survival. Future studies with cell-specific methodologies may yield targets for therapeutic strategies to improve cognitive dysfunction after TBI.