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Cited by 70Epilepsy research and treatmentTuberous Sclerosis Complex ResearchNeuroscience and Neuropharmacology Research

Mapping the spatio-temporal pattern of the mammalian target of rapamycin (mTOR) activation in temporal lobe epilepsy.

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Sha, Long-Ze, Xing, Xiao-Liang, Zhang, Dan, Yao, Yuan, Dou, Wan-Chen, Jin, Li-Ri, Wu, Li-Wen, Xu, Qi·2012·PLoS ONE
DOI 10.1371/journal.pone.0039152PMC PMC3384628
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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.

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  • mTOR hyperactivation accompanies epileptic activity across animal models of temporal lobe epilepsy, post-traumatic epilepsy, focal cortical dysplasia II, Dravet syndrome, autism spectrum disorder, and tuberous sclerosis complex.

    “Furthermore, mTOR hyperactivation accompanies epileptic activity across different seizure models including animal models of TLE, PTE, FCDII, Dravet syndrome, ASD, and TSC (Meikle et al., 2007; Zeng et al., 2008; Sha et al., 2012; Guo et al., 2013; Gheyara et al., 2014; Butler et al., 2015; Marsan and Baulac, 2018; Tai et al., 2020; Shao et al., 2022).”

    From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Sha et al., 2012

    The Introduction reports mTOR overactivation in rodent models of temporal lobe epilepsy, and the Discussion describes activation in the paper’s TLE mouse model. The paper also discusses a mouse model of tuberous sclerosis complex, but the cited passages do not support the claim across post-traumatic epilepsy, focal cortical dysplasia II, Dravet syndrome, or autism spectrum disorder models. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Sha, L.-Z., Xing, X.-L., Zhang, D., Yao, Y., Dou, W.-C., Jin, L.-R., Wu, L.-W., & Xu, Q.
Affiliations
  • Sir Run Run Shaw Hospital (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Xu, Qi
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-06-27
Volume
7
Issue
6
Pages
e39152
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0039152
PMC
PMC3384628
OpenAlex
W1976984689
Cited by
70
References
1
Citations by year
2026: 1 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 4
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31021091, 30971001)
  • Peking Union Medical College Hospital
  • Peking Union Medical College
  • Fok Ying Tong Education Foundation (121024)
  • National Key Research and Development Program of China (2010CB529603, 2012CB517902)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
mTOR signaling, temporal lobe epilepsy, epileptogenesis, drug-resistant epilepsy, reactive astrocytes, granule cells, kainate-induced seizures, cell type-specific signaling, granular layer
MeSH terms
Adult, Animals, Astrocytes, Disease Models, Animal, Electroencephalography, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Immunoenzyme Techniques, Kainic Acid, Male, Mice, Inbred C57BL, Middle Aged, Neurons, Sclerosis, Seizures, Signal Transduction, Case-Control Studies, Excitatory Amino Acid Agonists, Mice, Young Adult, TOR Serine-Threonine Kinases

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