PMID- 21307269
OWN - NLM
STAT- MEDLINE
DCOM- 20110325
LR  - 20220408
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 31
IP  - 6
DP  - 2011 Feb 9
TI  - Rapamycin suppresses mossy fiber sprouting but not seizure frequency in a mouse 
      model of temporal lobe epilepsy.
PG  - 2337-47
LID - 10.1523/JNEUROSCI.4852-10.2011 [doi]
AB  - Temporal lobe epilepsy is prevalent and can be difficult to treat effectively. 
      Granule cell axon (mossy fiber) sprouting is a common neuropathological finding 
      in patients with mesial temporal lobe epilepsy, but its role in epileptogenesis 
      is unclear and controversial. Focally infused or systemic rapamycin inhibits the 
      mammalian target of rapamycin (mTOR) signaling pathway and suppresses mossy fiber 
      sprouting in rats. We tested whether long-term systemic treatment with rapamycin, 
      beginning 1 d after pilocarpine-induced status epilepticus in mice, would 
      suppress mossy fiber sprouting and affect the development of spontaneous 
      seizures. Mice that had experienced status epilepticus and were treated for 2 
      months with rapamycin displayed significantly less mossy fiber sprouting (42% of 
      vehicle-treated animals), and the effect was dose dependent. However, behavioral 
      and video/EEG monitoring revealed that rapamycin- and vehicle-treated mice 
      displayed spontaneous seizures at similar frequencies. These findings suggest 
      mossy fiber sprouting is neither pro- nor anti-convulsant; however, there are 
      caveats. Rapamycin treatment also reduced epilepsy-related hypertrophy of the 
      dentate gyrus but did not significantly affect granule cell proliferation, hilar 
      neuron loss, or generation of ectopic granule cells. These findings are 
      consistent with the hypotheses that hilar neuron loss and ectopic granule cells 
      might contribute to temporal lobe epileptogenesis.
FAU - Buckmaster, Paul S
AU  - Buckmaster PS
AD  - Department of Comparative Medicine, Stanford University, Stanford, California 
      94305, USA. psb@stanford.edu
FAU - Lew, Felicia H
AU  - Lew FH
LA  - eng
GR  - T35 RR017188/RR/NCRR NIH HHS/United States
GR  - T35 RR017188-09/RR/NCRR NIH HHS/United States
GR  - R01 NS039110/NS/NINDS NIH HHS/United States
GR  - R01 NS040276/NS/NINDS NIH HHS/United States
GR  - R01 NS040276-09S1/NS/NINDS NIH HHS/United States
GR  - T35 OD010989/OD/NIH HHS/United States
GR  - R01 NS040276-10/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Anticonvulsants)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Slc30a4 protein, mouse)
RN  - Q3JTX2Q7TU (Diazepam)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Anticonvulsants/therapeutic use
MH  - Cation Transport Proteins/metabolism
MH  - Diazepam/therapeutic use
MH  - Disease Models, Animal
MH  - Drug Administration Schedule
MH  - Electroencephalography/methods
MH  - Epilepsy, Temporal Lobe/drug therapy/*pathology/*physiopathology
MH  - Hippocampus/*drug effects/pathology
MH  - Immunosuppressive Agents/*pharmacology/therapeutic use
MH  - Mice
MH  - Mossy Fibers, Hippocampal/*drug effects/pathology/physiopathology
MH  - Neurons/drug effects/pathology
MH  - Seizures/drug therapy/etiology
MH  - Sirolimus/*pharmacology/therapeutic use
MH  - Videotape Recording/methods
PMC - PMC3073836
MID - NIHMS271056
EDAT- 2011/02/11 06:00
MHDA- 2011/03/26 06:00
PMCR- 2011/08/09
CRDT- 2011/02/11 06:00
PHST- 2011/02/11 06:00 [entrez]
PHST- 2011/02/11 06:00 [pubmed]
PHST- 2011/03/26 06:00 [medline]
PHST- 2011/08/09 00:00 [pmc-release]
AID - 31/6/2337 [pii]
AID - 3671001 [pii]
AID - 10.1523/JNEUROSCI.4852-10.2011 [doi]
PST - ppublish
SO  - J Neurosci. 2011 Feb 9;31(6):2337-47. doi: 10.1523/JNEUROSCI.4852-10.2011.