Increased Expression Of Notch1in Temporal Lobe Epilepsy:a Based Evidence In Animal And Human

Background:Notchl is a signaling protein that is crucial in regulating cell proliferation, differentiation, and neural progenitor cell survival during nervous system development. Recent evidence shows that the Notchl plays an important role in adulthood in regulating structural plasticity. Astrogliosis can be observed in epilepsy as a type of structural plasticity and be considered to be one of its causes. Here we investigated the expression of the Notchl, Notchl downstream protein Hesl and astrogliosis in epileptic temporal lobe epileptic foci in patients and experimental animals in order to explore the probable relationship between Notchl expression and temporal lobe epilepsy (TLE). Methods:The Notchl and Hesl expression was assessed in20human brain tissues derived from patients undergoing operation for intractable TLE and also detected in6histological normal temporal lobes from controls. Meanwhile, we investigated the Notchl, Hesl and glial fibrillary acidic portein (GFAP) expression in the temporal neocortex and hippocampus from the control group and lithium-pilocarpine-treated rats in without status epilepticus (SE) group, SE group, without spontaneous recurrent seizure (SRS) group, zileuton treated SRS group and vehicle SRS group. Expression of Notchl, Hesl and GFAP were assessed by immunohistochemistry. Meanwhile, electroencephalogram (EEG) and video observation were used as auxiliary measures. Results:In experimental rats, Notchl and Hesl were mainly expressed at CA1, CA3, dentate gyrus and the hilus. Meanwhile, the expression of Notchl, Hesl and GFAP were enhanced in SE and vehicle SRS groups. There was no obvious difference among the control group, without SE group, without SRS group and Zileuton treated SRS group. Compared to the control group, Notchl and Hesl expressie was enhanced in the temporal neocortex of patients with intractable TLE. Conclusion These results suggest that Notchl may play an important role in the development of TLE and indicate that block Notchl signaling may be a potential treatment for TLE.