Transcriptome Analysis of the Hippocampus in Novel Rat Model of Febrile Seizures

Abstract

Febrile seizures (FS) are the most common type of convulsive events in infants and young children, but the precise underlying genetic mechanism remains to be explored. To investigate the underlying pathogenic factors in FS and subsequent epilepsy, alterations in gene expression between the two new strains of rats (hyperthermia-prone [HP] vs hyperthermia-resistant [HR]), were investigated by using the Whole Rat Genome Oligo Microarray. This process identified 1,140 differentially expressed genes (DEGs; 602 upregulated and 538 downregulated), which were analyzed to determine significant Gene Ontology (GO) categories, signaling pathways and gene networks. Based on the GO analyses, the modified genes are closely related to various FS pathogenesis factors, including immune and inflammatory responses and ion transport. Certain DEGs identified have not been previously examined in relation to FS pathogenesis. Among these genes is dipeptidyl peptidase 4 (DPP4), a gene closely linked to interleukin 6 (IL-6), which played a key role in the gene network analysis. Furthermore, sitagliptin, a DPP4 inhibitor significantly decreased epileptic discharge in rats, observed via electroencephalogram, suggesting an important role for DPP4 in FS. The effectiveness of sitagliptin in reducing seizure activity may occur through a mechanism that stabilizes cellular Ca2+ homeostasis. In addition, DPP4 expression may be regulated by DNA methylation. The hippocampal gene expression profiles in novel rat models of FS provides a large database of candidate genes and pathways, which will be useful for researchers interested in disorders of neuronal excitability.

De Novo Transcriptome Assembly of the Chinese Swamp Buffalo by RNA Sequencing and SSR Marker Discovery

“…The high demand for low-cost sequencing has led to the development of high-throughput technologies such as next-generation sequencing [ 50 ]. Transcriptome sequencing is one such powerful and cost-effective tool in generating large-scale transcriptome data that may be used in developing molecular markers and in identifying novel genes in model [ 35 , 51 ] and non-model [ 52 , 53 ] organisms. To our knowledge, the present study is the first attempt to perform de novo assembly and to conduct a comprehensive characterization of the comprehensive transcripts of swamp buffalo.…”

Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the Hippocampus

“…Genes important in these processes included, CCL-2 , CCL-3 , ILr10-a /b, C1qa , and Cr1l . Febrile seizures in rats also show a robust immune response directly after exposure to HT [ 49 , 55 ]. Similarly, electrical kindling of the dentate gyrus as a model for TLE, showed overlap in biological processes with our genelists.…”

Long-term metabolic alterations in a febrile seizure model

“…Previous studies have suggested that HP rats have a low seizure threshold and experience spontaneous seizures [19]; the low seizure threshold might be associated with the expression levels and patterns of numerous genes, including a group of metabolism-related genes [20].…”

“…Using this rat model, we identified numerous FS susceptibility genes related to metabolism [20]. In this study, we measured particular metabolic parameters and the expression of key genes that are related to metabolism in HP and wild-type (WT) rats.…”