title: Notch signaling activation promotes seizure activity in temporal lobe epilepsy.
abstract: Notch signaling in the nervous system is often regarded as a developmental pathway. However, recent studies have suggested that Notch is associated with neuronal discharges. Here, focusing on temporal lobe epilepsy, we found that Notch signaling was activated in the kainic acid (KA)-induced epilepsy model and in human epileptogenic tissues. Using an acute model of seizures, we showed that DAPT, an inhibitor of Notch, inhibited ictal activity. In contrast, pretreatment with exogenous Jagged1 to elevate Notch signaling before KA application had proconvulsant effects. In vivo, we demonstrated that the impacts of activated Notch signaling on seizures can in part be attributed to the regulatory role of Notch signaling on excitatory synaptic activity in CA1 pyramidal neurons. In vitro, we found that DAPT treatment impaired synaptic vesicle endocytosis in cultured hippocampal neurons. Taken together, our findings suggest a correlation between aberrant Notch signaling and epileptic seizures. Notch signaling is up-regulated in response to seizure activity, and its activation further promotes neuronal excitation of CA1 pyramidal neurons in acute seizures.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730.
authors.forename: Longze
authors.initials: L
authors.lastname: Sha
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Sha
authors.forename: Xueqin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Xing
authors.forename: Wanchen
authors.initials: W
authors.lastname: Dou
authors.forename: Liri
authors.initials: L
authors.lastname: Jin
authors.forename: Wenting
authors.initials: W
authors.lastname: Li
authors.forename: Naili
authors.initials: N
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.forename: Liwen
authors.initials: L
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D051881:Receptor, Notch1 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D007608:Kainic Acid