GENE EXPRESSION ALTERATIONS IN CA1 AREA OF THE RAT HIPPOCAMPUS BEFORE THE ONSET OF EPILEPSY: A MICROCHIP STUDY
Abstract number :
2.077
Submission category :
Year :
2003
Submission ID :
2253
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Tatiana Y. Rikhter, Fu-Chun Hsu, Douglas A. Coulter Neurology, Children[apos]s Hospital of Philadelphia, UPenn School of Medicine, Philadelphia, PA; Pediatrics, Neuroscience, Neurology, UPenn School of Medicine, Philadelphia, PA
The latent period is characteristic for most symptomatic epilepsies, including temporal lobe epilepsy (TLE), although little is known about specific cellular, molecular and anatomical mechanisms leading to the clinical onset of the disease. The latent period is defined as an interval after a precipitating event and before the onset of spontaneous recurrent seizures, may last weeks in animals and months/years in humans. We previously identified multiple Status Epilepticus (SE)-induced gene expression alterations in the dentate gyrus of rats 2 hours-7 days post pilocarpine-induced SE. The goal of the present study was to determine gene expression alterations in the CA1 area of post-SE rats within the same time frame using microchip technology.
Total RNA was isolated from CA1 area of control, 2h, 24h and 7 days post pilocarpine-induced SE rats (n=4 each). cRNA was made and hybridized to RN-U34 arrays (Affymetrix) according to manufacturer[rsquo]s protocol. Data analysis was performed using GeneSpring software.
Altered expression was defined as increase:[gt]150% of control; decrease:[lt]50% of control. At 2h, 24h and 7d post SE, increased expression was detected for t-PA, ICAM-1, Hmox1 and Scya2 genes. At both 2h and 24h post SE, expression increase was detected for Nf[kappa]b1, HSP70.2, HSP70.1, VGF, c-jun, c-fos and gag-fos genes. At both 24h and 7d post SE, expression increase was detected for ania4, metallothionein, Il18, Hsp27, peripheral benzodiazepine receptor, prostaglandin F receptor, nestin and vimentin genes. Decreased were GABAR [alpha]5, Gria2, 5HT5b, cannabinoid receptor 1, c-kit receptor tyrosine kinase and protein kinase C type I genes. Some of the gene expression alterations were characteristic for CA1 and not for DG (2h - Nf[kappa]b1, t-PA, VGF, Hmox1, HSP70.1, NOR-2; 24h - prostaglandin F receptor, HSP70.2, Gria2, neurotrimin, synuclein; 7d - ania4, metallothionein, cannabinoid receptor 1, Gria2, protein kinase C type I, t-PA, Hsp27, nestin, vimentin, ICAM-1, Scya2, Il18, Hmox1, peripheral benzodiazepine receptor, SNAP-25A). Expression of transcription factors/immediate early genes and receptors/channels was most affected by SE. Cluster analysis revealed potential co-regulated genes with related functions.
SE alters expression of many genes important in cell physiology including transcription factors, receptors and channels, neuropeptides and kinases. A subset of SE-induced gene expression alterations is different from those in DG and specific for CA1. The identification of these distinct CA1 gene expression alterations may help to decipher the unique role of CA1 in the latent period of TLE.
[Supported by: DAC: NIH-NINDS32403, NIH-NINDS38572.]