Possible role of the innate immunity in temporal lobe epilepsy.
OBJECTIVE
Temporal lobe epilepsy (TLE) is a multifactorial disease often involving the hippocampus. So far the etiology of the disease has remained elusive. In some pharmacoresistant TLE patients the hippocampus is surgically resected as treatment. To investigate the involvement of the immune system in human TLE, we performed large-scale gene expression profiling on this human hippocampal tissue.


METHODS
Microarray analysis was performed on hippocampal specimen from TLE patients with and without hippocampal sclerosis and from autopsy controls (n = 4 per group). We used a common reference pool design to perform an unbiased three-way comparison between the two patient groups and the autopsy controls. Differentially expressed genes were statistically analyzed for significant overrepresentation of gene ontology (GO) classes.


RESULTS
Three-way analysis identified 618 differentially expressed genes. GO analysis identified immunity and defense genes as most affected in TLE. Particularly, the chemokines CCL3 and CCL4 were highly (>10-fold) upregulated. Other highly affected gene classes include neuropeptides, chaperonins (protein protection), and the ubiquitin/proteasome system (protein degradation).


CONCLUSIONS
The strong upregulation of CCL3 and CCL4 implicates these chemokines in the etiology and pathogenesis of TLE. These chemokines, which are mainly expressed by glia, may directly or indirectly affect neuronal excitability. Genes and gene clusters identified here may provide targets for developing new TLE therapies and candidates for genetic research.
van Gassen
Koen L I
KL
Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
de Wit
Marina
M
Koerkamp
Marian J A Groot
MJ
Rensen
Marije G A
MG
van Rijen
Peter C
PC
Holstege
Frank C P
FC
Lindhout
Dick
D
de Graan
Pierre N E
PN
D000328:Adult; D038481:Anterior Temporal Lobectomy; D054405:Chemokine CCL3 / Q000235:genetics; D054407:Chemokine CCL4 / Q000235:genetics; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000276:immunology / Q000473:pathology / Q000601:surgery; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics
D054405:Chemokine CCL3; D054407:Chemokine CCL4