Gene Expression in Temporal Lobe Epilepsy is Consistent with Increased Release of Glutamate by Astrocytes

摘要: Patients with temporal lobe epilepsy (TLE) often have a shrunken hippocampus that is known to be the location in which seizures originate. The role of sclerotic causation and maintenance has remained incompletely understood despite extensive neuropathological investigations this substrate. To gain new insights develop testable hypotheses on sclerosis pathophysiology TLE, differential gene expression profile was studied. end, DNA microarray analysis used compare profiles non-sclerotic hippocampi surgically removed from TLE patients. Sclerotic had transcriptional signatures were different hippocampi. differentially expressed set revealed changes several molecular signaling pathways, included increased genes associated astrocyte structure (glial fibrillary acidic protein, ezrin-moesin-radixin, palladin), calcium regulation (S100 binding protein beta, chemokine (C-X-C motif) receptor 4) blood-brain barrier function (Aquaaporin 4, Chemokine (C-C-motif) ligand 2, 3, Plectin 1, intermediate filament 55kDa) inflammatory responses. Immunohistochemical localization studies show there altered distribution gene-associated proteins astrocytes foci compared foci. It hypothesized tissue activated pathways could lead enhanced release glutamate by these cells. Such may excite surrounding neurons elicit seizure activity.