title: 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.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Yuanteng
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Duanhe
authors.initials: D
authors.lastname: Heng
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000188:drug therapy / Q000235:genetics*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate
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