Dataset Information

RNAseq analysis of hippocampal microglia after kainic acid-induced seizures.

ABSTRACT: Microglia have been shown to be of critical importance to the progression of temporal lobe epilepsy. However, the broad transcriptional changes that these cells undergo following seizure induction is not well understood. As such, we utilized RNAseq analysis upon microglia isolated from the hippocampus to determine expression pattern alterations following kainic acid induced seizure. We determined that microglia undergo dramatic changes to their expression patterns, particularly with regard to mitochondrial activity and metabolism. We also observed that microglia initiate immunological activity, specifically increasing interferon beta responsiveness. Our results provide novel insights into microglia transcriptional regulation following acute seizures and suggest potential therapeutic targets specifically in microglia for the treatment of seizures and epilepsy.

SUBMITTER: Bosco DB

PROVIDER: S-EPMC6011524 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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RNAseq analysis of hippocampal microglia after kainic acid-induced seizures.

Bosco Dale B DB Zheng Jiaying J Xu Zhiyan Z Peng Jiyun J Eyo Ukpong B UB Tang Ke K Yan Cheng C Huang Jun J Feng Lijie L Wu Gongxiong G Richardson Jason R JR Wang Hui H Wu Long-Jun LJ

Molecular brain 20180620 1

Microglia have been shown to be of critical importance to the progression of temporal lobe epilepsy. However, the broad transcriptional changes that these cells undergo following seizure induction is not well understood. As such, we utilized RNAseq analysis upon microglia isolated from the hippocampus to determine expression pattern alterations following kainic acid induced seizure. We determined that microglia undergo dramatic changes to their expression patterns, particularly with regard to mi ...[more]

PMID: 29925434

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Project description:Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA)-induced status epilepticus (SE) in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed), and long-term potentiation (LTP; 18 genes changed). Also genes involved in Ca(2+) homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP), apolipoprotein E (apo E), cannabinoid type 1 receptor (CB1), Purkinje cell protein 4 (PEP-19), and interleukin 8 receptor (CXCR1), with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE). However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the juvenile age group.

Dataset Information

RNAseq analysis of hippocampal microglia after kainic acid-induced seizures.

Publications

RNAseq analysis of hippocampal microglia after kainic acid-induced seizures.

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