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Notch Signaling Activation Promotes Seizure Activity in Temporal Lobe Epilepsy

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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.

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Acknowledgments

We sincerely thank all the patients for their support and participation. We thank Prof. Jun Wei for revising of the manuscript. This work was supported by the National Basic Research Program of China [2010CB529603, 2012CB517902], National Natural Science Foundation of China [30971001, 31222031, 31021091], Bei**g Natural Science Foundation [7102109], and Fok Ying Tong Education Foundation [121024].

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei**g, China, 100730

    Longze Sha, **aofeng Wu, Zhiqiang Sha, Xueqin Wang, **aoliang **ng, Wenting Li, Naili Wang, Yan Shen & Qi Xu

  2. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei**g, China, 100730

    Yuan Yao, Wanchen Dou, Liri ** & Liwen Wu

  3. State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Bei**g, China, 100101

    Bo Wen, **g Feng & **hui Wang

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  1. Longze Sha
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Correspondence to Qi Xu.

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Authors Longze Sha and **aofeng Wu contributed equally to this work.

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Sha, L., Wu, X., Yao, Y. et al. Notch Signaling Activation Promotes Seizure Activity in Temporal Lobe Epilepsy. Mol Neurobiol 49, 633–644 (2014). https://doi.org/10.1007/s12035-013-8545-0

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