Notch Signaling Activation Promotes Seizure Activity in Temporal Lobe Epilepsy

• Published in: Molecular neurobiology 2014-04, Vol.49 (2), p.633-644
• Main Authors: Sha, Longze, Wu, Xiaofeng, Yao, Yuan, Wen, Bo, Feng, Jing, Sha, Zhiqiang, Wang, Xueqin, Xing, Xiaoliang, Dou, Wanchen, Jin, Liri, Li, Wenting, Wang, Naili, Shen, Yan, Wang, Jinhui, Wu, Liwen, Xu, Qi
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; Cell Biology; Cells, Cultured; Convulsions & seizures; Epilepsy; Epilepsy, Temporal Lobe - metabolism; Epilepsy, Temporal Lobe - pathology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Humans; Kainic Acid - toxicity; Male; Mice, Inbred C57BL; Neurobiology; Neurology; Neurosciences; Organ Culture Techniques; Receptor, Notch1 - metabolism; Seizures - chemically induced; Seizures - metabolism; Seizures - pathology; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-013-8545-0

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.