PMID- 22242835
OWN - NLM
STAT- MEDLINE
DCOM- 20120423
LR  - 20220330
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 53
IP  - 3
DP  - 2012 Mar
TI  - Pentylenetetrazole-induced seizures cause acute, but not chronic, mTOR pathway 
      activation in rat.
PG  - 506-11
LID - 10.1111/j.1528-1167.2011.03384.x [doi]
AB  - PURPOSE: The mammalian target of rapamycin (mTOR) pathway has been implicated in 
      contributing to progressive epileptogenesis in models of chronic epilepsy. 
      Conversely, seizures themselves may directly cause acute activation of the mTOR 
      pathway. To isolate the direct effects of seizures on the mTOR pathway, the time 
      course and mechanisms of mTOR activation were investigated with acute seizures 
      induced by pentylenetetrazole (PTZ), which does not lead to chronic epilepsy. 
      METHODS: Western blot analysis was used to assay the phosphorylation of Akt and 
      S6, as measures of activation of the phosphoinositide 3-kinase (PI3K)/Akt and 
      mTOR pathways, respectively, at various time points after PTZ-induced seizures in 
      rats. The ability of wortmannin, a PI3K inhibitor, to inhibit PTZ seizure-induced 
      activation of the mTOR pathway was tested. KEY FINDINGS: PTZ-induced seizures 
      produced an immediate, transient mTOR activation lasting several hours, but no 
      later, more chronic activation over days to weeks. This acute stimulation of the 
      mTOR pathway by PTZ-induced seizures was mediated by upstream PI3K/Akt pathway 
      activation and was blocked by a PI3K inhibitor. SIGNIFICANCE: Compared with 
      models of chronic epilepsy that exhibit biphasic (acute and chronic) mTOR pathway 
      activation, PTZ-induced seizures produce only acute, but not chronic, mTOR 
      activation. These results in the PTZ seizure model highlight potential 
      differences in the involvement of the mTOR pathway between self-limited seizures 
      and progressive epileptogenesis. These findings also suggest a potential 
      therapeutic role of PI3K inhibitors in epilepsy.
CI  - Wiley Periodicals, Inc. (c) 2012 International League Against Epilepsy.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Department of Neurology and the Hope Center for Neurological Disorders, 
      Washington University School of Medicine, St. Louis, MO, USA.
FAU - Wong, Michael
AU  - Wong M
LA  - eng
GR  - R01 NS056872/NS/NINDS NIH HHS/United States
GR  - R01 NS056872-06/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120113
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Convulsants)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - WM5Z385K7T (Pentylenetetrazole)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Chronic Disease
MH  - Convulsants/toxicity
MH  - Disease Models, Animal
MH  - Enzyme Activation/drug effects/physiology
MH  - Epilepsy/chemically induced/*metabolism/*physiopathology
MH  - Male
MH  - Pentylenetetrazole/administration & dosage/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases/*metabolism/physiology
PMC - PMC3290678
MID - NIHMS343132
EDAT- 2012/01/17 06:00
MHDA- 2012/04/24 06:00
PMCR- 2013/03/01
CRDT- 2012/01/17 06:00
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/04/24 06:00 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - 10.1111/j.1528-1167.2011.03384.x [doi]
PST - ppublish
SO  - Epilepsia. 2012 Mar;53(3):506-11. doi: 10.1111/j.1528-1167.2011.03384.x. Epub 
      2012 Jan 13.