Correlated stage- and subfield-associated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy.
Epileptic activity evokes profound alterations of hippocampal organization and function. Genomic responses may reflect immediate consequences of excitatory stimulation as well as sustained molecular processes related to neuronal plasticity and structural remodeling. Using oligonucleotide microarrays with 8799 sequences, we determined subregional gene expression profiles in rats subjected to pilocarpine-induced epilepsy (U34A arrays, Affymetrix, Santa Clara, CA, USA; P < 0.05, twofold change, n = 3 per stage). Patterns of gene expression corresponded to distinct stages of epilepsy development. The highest number of differentially expressed genes (dentate gyrus, approx. 400 genes and CA1, approx. 700 genes) was observed 3 days after status epilepticus. The majority of up-regulated genes was associated with mechanisms of cellular stress and injury - 14 days after status epilepticus, numerous transcription factors and genes linked to cytoskeletal and synaptic reorganization were differentially expressed and, in the stage of chronic spontaneous seizures, distinct changes were observed in the transcription of genes involved in various neurotransmission pathways and between animals with low vs. high seizure frequency. A number of genes (n = 18) differentially expressed during the chronic epileptic stage showed corresponding expression patterns in hippocampal subfields of patients with pharmacoresistant temporal lobe epilepsy (n = 5 temporal lobe epilepsy patients; U133A microarrays, Affymetrix; covering 22284 human sequences). These data provide novel insights into the molecular mechanisms of epileptogenesis and seizure-associated cellular and structural remodeling of the hippocampus.
Becker
Albert J
AJ
Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Strasse 25, D-53105 Bonn, Germany. albert_becker@uni-bonn.de
Chen
Jian
J
Zien
Alexander
A
Sochivko
Dmitry
D
Normann
Sabine
S
Schramm
Johannes
J
Elger
Christian E
CE
Wiestler
Otmar D
OD
Blümcke
Ingmar
I
D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010862:Pilocarpine / Q000031:analogs & derivatives*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D012333:RNA, Messenger; D010862:Pilocarpine; C029118:pilocarpic acid