Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.
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.
Laurén
Hanna B
HB
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland.
Lopez-Picon
Francisco R
FR
Brandt
Annika M
AM
Rios-Rojas
Clarissa J
CJ
Holopainen
Irma E
IE
D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D007608:Kainic Acid; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D042282:Microdissection; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D009435:Synaptic Transmission / Q000235:genetics
D002135:Calcium-Binding Proteins; D007608:Kainic Acid