Notch Signaling Activation Promotes Seizure Activity in Temporal Lobe Epilepsy

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-013-8545-0