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

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 use...

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Published in:PloS one 2012-06, Vol.7 (6), p.e39152
Main Authors: Sha, Long-Ze, Xing, Xiao-Liang, Zhang, Dan, Yao, Yuan, Dou, Wan-Chen, Jin, Li-Ri, Wu, Li-Wen, Xu, Qi
Format: Article
Language:English
Subjects:
Adult
Animal models
Animals
Astrocytes
Astrocytes - metabolism
Astrocytes - pathology
Biology
Brain
Brain cancer
Case-Control Studies
Cell activation
Cell body
Disease Models, Animal
Dispersion
Drug resistance
Electroencephalography
Epilepsy
Epilepsy, Temporal Lobe - metabolism
Epilepsy, Temporal Lobe - pathology
Ethics
Excitatory Amino Acid Agonists - toxicity
Female
Glioma
Granular materials
Granule cells
Hippocampus
Hippocampus - metabolism
Hippocampus - pathology
Hospitals
Humans
Hypertrophy
Immunoenzyme Techniques
Kainic Acid - toxicity
Laboratory animals
Male
Mammals
Medicine
Mice
Mice, Inbred C57BL
Middle Aged
Molecular biology
Neural networks
Neurology
Neurons
Neurons - metabolism
Neurons - pathology
Neurosciences
Patients
Rapamycin
Rodents
Science
Sclerosis - metabolism
Sclerosis - pathology
Seizures
Seizures (Medicine)
Seizures - chemically induced
Seizures - metabolism
Seizures - pathology
Signal Transduction
Signaling
Studies
Temporal lobe
Temporal lobe epilepsy
TOR protein
TOR Serine-Threonine Kinases - metabolism
Trends
Young Adult
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039152