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The implications of hippocampal neurogenesis in adolescent rats after status epilepticus: a novel role of notch signaling pathway in regulating epileptogenesis

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Abstract

Seizure-induced neurogenesis has a widely recognized pro-epileptogenic function. Given the critical role of Notch signaling during the maintenance and neurogenesis of neural stem cells, we hypothesized that Notch may affect epileptogenesis and its progression through its role in neurogenesis in the adolescent rat brain. We used the lithium-pilocarpine-induced epilepsy model in adolescent Sprague–Dawley rats in order to evaluate hippocampal neurogenesis and epileptogenesis following the onset of status epilepticus (SE). We used western blotting analyses and qPCR to measure levels of Notch signaling at different phases after seizures and immunofluorescence to detect the proliferation and differentiation of neural stem cells after seizure. Following the administration of DAPT, a Notch γ-secretase inhibitor, into the lateral ventricles, we observed a suppression of abnormal neurogenesis in the acute phase and a reduction of gliosis in the chronic phase after SE. Accordingly, the frequency and duration of spontaneous seizures in chronic phase were decreased. Our results clarify the basic concept regarding the involvement of Notch signaling in the regulation of hippocampal neurogenesis and epileptogenesis, thereby potentially offering a novel and alternative treatment for epilepsy.

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Funding

This work was supported by the National Natural Science Foundation of China (NSFC Grant 81501056).

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Authors and Affiliations

  1. Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children’s Hospital of Chongqing Medical UniSversity, Chongqing, People’s Republic of China

    Ping Yuan, Wei Han, Lingling Xie, Li Cheng, Hengsheng Chen, Jin Chen & Li Jiang

  2. Department of Neurology, Children’s Hospital of Chongqing Medical University, 136# Zhongshan 2nd Road, YuZhong District, Chongqing, 400014, People’s Republic of China

    Ping Yuan, Wei Han, Lingling Xie, Jin Chen & Li Jiang

Authors
  1. Ping Yuan
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  2. Wei Han
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  3. Lingling Xie
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  4. Li Cheng
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  5. Hengsheng Chen
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  6. Jin Chen
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  7. Li Jiang
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Contributions

Ping Yuan, Jin Chen and Li Jiang conceived and designed the experiments. Ping Yuan performed the experiments and analyzed the data. Lingling Xie, Wei Han, Li Cheng and Hengsheng Chen contributed reagents, materials and analytical tools. Ping Yuan wrote the manuscript.

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Correspondence to Jin Chen or Li Jiang.

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The authors declare that they have no conflict of interest.

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All protocols were executed according to NIH Guidelines regarding the care and use of laboratory animals and approved and monitored by the Animal Care Committee of Chongqing Medical University, Chongqing, China.

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Yuan, P., Han, W., Xie, L. et al. The implications of hippocampal neurogenesis in adolescent rats after status epilepticus: a novel role of notch signaling pathway in regulating epileptogenesis. Cell Tissue Res 380, 425–433 (2020). https://doi.org/10.1007/s00441-019-03146-z

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  • DOI: https://doi.org/10.1007/s00441-019-03146-z

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