PMID- 23724051
OWN - NLM
STAT- MEDLINE
DCOM- 20140110
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Spatiotemporal characterization of mTOR kinase activity following kainic acid 
      induced status epilepticus and analysis of rat brain response to chronic 
      rapamycin treatment.
PG  - e64455
LID - 10.1371/journal.pone.0064455 [doi]
LID - e64455
AB  - Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient 
      availability, trophic factors support, cellular energy level, cellular stress, 
      and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR 
      activity is needed for development as well as proper physiology of mature 
      neurons. Consequently, changes in mTOR activity are often observed in 
      neuropathology. Recently, several groups reported that seizures increase 
      mammalian target of rapamycin (mTOR) kinase activity, and such increased activity 
      in genetic models can contribute to spontaneous seizures. However, the current 
      knowledge about the spatiotemporal pattern of mTOR activation induced by 
      proconvulsive agents is rather rudimentary. Also consequences of insufficient 
      mTOR activity on a status epilepticus are poorly understood. Here, we 
      systematically investigated these two issues. We showed that mTOR signaling was 
      activated by kainic acid (KA)-induced status epilepticus through several brain 
      areas, including the hippocampus and cortex as well as revealed two waves of mTOR 
      activation: an early wave (2 h) that occurs in neurons and a late wave that 
      predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with 
      rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA 
      treatment and (ii) induced gross anatomical changes in the brain.
FAU - Macias, Matylda
AU  - Macias M
AD  - Laboratory of Molecular and Cell Neurobiology, International Institute of 
      Molecular and Cell Biology, Warsaw, Poland.
FAU - Blazejczyk, Magdalena
AU  - Blazejczyk M
FAU - Kazmierska, Paulina
AU  - Kazmierska P
FAU - Caban, Bartosz
AU  - Caban B
FAU - Skalecka, Agnieszka
AU  - Skalecka A
FAU - Tarkowski, Bartosz
AU  - Tarkowski B
FAU - Rodo, Anna
AU  - Rodo A
FAU - Konopacki, Jan
AU  - Konopacki J
FAU - Jaworski, Jacek
AU  - Jaworski J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130528
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ribosomal Protein S6)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - SIV03811UC (Kainic Acid)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism/pathology
MH  - Brain/drug effects/enzymology/*pathology
MH  - Cell Death/drug effects
MH  - Cell Nucleus/drug effects/enzymology
MH  - Hippocampus/drug effects/pathology
MH  - Kainic Acid
MH  - Male
MH  - Neurons/drug effects/enzymology
MH  - Phosphorylation/drug effects
MH  - Phosphoserine/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Ribosomal Protein S6/metabolism
MH  - Seizures/drug therapy/pathology
MH  - Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage/pharmacology/*therapeutic use
MH  - *Spatio-Temporal Analysis
MH  - Status Epilepticus/chemically induced/*drug therapy/*enzymology/pathology
MH  - Subcellular Fractions/drug effects/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3665782
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/06/01 06:00
MHDA- 2014/01/11 06:00
PMCR- 2013/05/28
CRDT- 2013/06/01 06:00
PHST- 2012/10/11 00:00 [received]
PHST- 2013/04/15 00:00 [accepted]
PHST- 2013/06/01 06:00 [entrez]
PHST- 2013/06/01 06:00 [pubmed]
PHST- 2014/01/11 06:00 [medline]
PHST- 2013/05/28 00:00 [pmc-release]
AID - PONE-D-12-31203 [pii]
AID - 10.1371/journal.pone.0064455 [doi]
PST - epublish
SO  - PLoS One. 2013 May 28;8(5):e64455. doi: 10.1371/journal.pone.0064455. Print 2013.