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Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients
Published on: December 18, 2016
Mapping the spatio-temporal pattern of the mammalian target of rapamycin (mTOR) activation in temporal lobe epilepsy
Long-Ze Sha1, Xiao-Liang Xing, Dan Zhang
1National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Growing evidence from rodent models of temporal lobe epilepsy (TLE) indicates that dysregulation of the mammalian target of rapamycin (mTOR) pathway is involved in seizures and epileptogenesis. However, the role of the mTOR pathway in the epileptogenic process remains poorly understood. Here, we used an animal model of TLE and sclerotic hippocampus from patients with refractory TLE to determine whether cell-type specific activation of mTOR signaling occurs during each stage of epileptogenesis. In the TLE mouse model, we found that hyperactivation of the mTOR pathway is present in distinct hippocampal subfields at three different stages after kainate-induced seizures, and occurs in neurons of the granular and pyramidal cell layers, in reactive astrocytes, and in dispersed granule cells, respectively. In agreement with the findings in TLE mice, upregulated mTOR was observed in the sclerotic hippocampus of TLE patients. All sclerotic hippocampus (n = 13) exhibited widespread reactive astrocytes with overactivated mTOR, some of which invaded the dispersed granular layer. Moreover, two sclerotic hippocampus exhibited mTOR activation in some of the granule cells, which was accompanied by cell body hypertrophy. Taken together, our results indicate that mTOR activation is most prominent in reactive astrocytes in both an animal model of TLE and the sclerotic hippocampus from patients with drug resistant TLE.
Insights
Dysregulation of the mammalian target of rapamycin (mTOR) pathway contributes to temporal lobe epilepsy (TLE). This study reveals mTOR activation primarily in reactive astrocytes within TLE models and patient hippocampi, implicating astrocytes in epileptogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Epilepsy Research
Background:
- The mammalian target of rapamycin (mTOR) pathway is implicated in temporal lobe epilepsy (TLE) pathogenesis.
- The precise role and cell-type specific activation of mTOR signaling during epileptogenesis are not fully understood.
Purpose of the Study:
- To investigate cell-type specific mTOR signaling activation across different stages of epileptogenesis.
- To compare mTOR pathway activation in an animal model of TLE with human TLE patient samples.
Main Methods:
- Utilized a kainate-induced TLE mouse model.
- Analyzed hippocampal tissue from TLE patients with refractory epilepsy.
- Examined mTOR pathway activation in neurons and reactive astrocytes at distinct epileptogenic stages.
Main Results:
- Hyperactivation of the mTOR pathway was observed in specific hippocampal subfields and cell types (neurons, reactive astrocytes, dispersed granule cells) at different stages post-seizure in the TLE mouse model.
- Upregulated mTOR signaling was confirmed in the sclerotic hippocampus of TLE patients.
- Reactive astrocytes with overactivated mTOR were widespread in human TLE hippocampi, with some invading the granular layer.
Conclusions:
- mTOR pathway activation is a key feature of epileptogenesis in TLE.
- The study highlights prominent mTOR activation in reactive astrocytes in both TLE animal models and human drug-resistant TLE.
- Reactive astrocytes represent a significant cellular component involved in mTOR-mediated epileptogenic processes.
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