PMID- 22761730
OWN - NLM
STAT- MEDLINE
DCOM- 20130326
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - Mapping the spatio-temporal pattern of the mammalian target of rapamycin (mTOR) 
      activation in temporal lobe epilepsy.
PG  - e39152
LID - 10.1371/journal.pone.0039152 [doi]
LID - e39152
AB  - 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.
FAU - Sha, Long-Ze
AU  - Sha LZ
AD  - National Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 
      Beijing, China.
FAU - Xing, Xiao-Liang
AU  - Xing XL
FAU - Zhang, Dan
AU  - Zhang D
FAU - Yao, Yuan
AU  - Yao Y
FAU - Dou, Wan-Chen
AU  - Dou WC
FAU - Jin, Li-Ri
AU  - Jin LR
FAU - Wu, Li-Wen
AU  - Wu LW
FAU - Xu, Qi
AU  - Xu Q
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120627
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Astrocytes/*metabolism/pathology
MH  - Case-Control Studies
MH  - Disease Models, Animal
MH  - Electroencephalography
MH  - Epilepsy, Temporal Lobe/*metabolism/pathology
MH  - Excitatory Amino Acid Agonists/toxicity
MH  - Female
MH  - Hippocampus/*metabolism/pathology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Kainic Acid/toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Neurons/*metabolism/pathology
MH  - Sclerosis/*metabolism/pathology
MH  - Seizures/chemically induced/metabolism/pathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Young Adult
PMC - PMC3384628
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/07/05 06:00
MHDA- 2013/03/27 06:00
PMCR- 2012/06/27
CRDT- 2012/07/05 06:00
PHST- 2012/03/15 00:00 [received]
PHST- 2012/05/16 00:00 [accepted]
PHST- 2012/07/05 06:00 [entrez]
PHST- 2012/07/05 06:00 [pubmed]
PHST- 2013/03/27 06:00 [medline]
PHST- 2012/06/27 00:00 [pmc-release]
AID - PONE-D-12-07902 [pii]
AID - 10.1371/journal.pone.0039152 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e39152. doi: 10.1371/journal.pone.0039152. Epub 2012 Jun 27.