PMID- 30132243
OWN - NLM
STAT- MEDLINE
DCOM- 20181105
LR  - 20220408
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 38
IP  - 7
DP  - 2018 Oct
TI  - Metformin Plus Caloric Restriction Show Anti-epileptic Effects Mediated by mTOR 
      Pathway Inhibition.
PG  - 1425-1438
LID - 10.1007/s10571-018-0611-8 [doi]
AB  - Caloric restriction (CR) has anti-epileptic effects in different animal models, 
      at least partially due to inhibition of the mechanistic or mammalian target of 
      rapamycin (mTOR) signaling pathway. Adenosine monophosphate-activated protein 
      kinase (AMPK) inhibits mTOR cascade function if energy levels are low. Since 
      hyper-activation of mTOR participates in epilepsy, its inhibition results in 
      beneficial anti-convulsive effects. A way to attain this is to activate AMPK with 
      metformin. The effects of metformin, alone or combined with CR, on the electrical 
      kindling epilepsy model and the mTOR cascade in the hippocampus and the neocortex 
      were studied. Combined metformin plus CR beneficially affected many kindling 
      aspects, especially those relating to generalized convulsive seizures. Therefore, 
      metformin plus CR could decrease measures of epileptic activity in patients with 
      generalized convulsive seizures. Patients that are obese, overweight or that have 
      metabolic syndrome in addition to having an epileptic disease are an ideal 
      population for clinical trials to test the effectiveness of metformin plus CR.
FAU - Rubio Osornio, Maria Del Carmen
AU  - Rubio Osornio MDC
AD  - Laboratorio de Neurofisiologia, Instituto Nacional de Neurologia y Neurocirugia, 
      Av. Insurgentes Sur 3877, Col. La Fama, Del. Tlalpan, 14269, Mexico City, Mexico.
FAU - Custodio Ramirez, Veronica
AU  - Custodio Ramirez V
AD  - Laboratorio de Neurofisiologia, Instituto Nacional de Neurologia y Neurocirugia, 
      Av. Insurgentes Sur 3877, Col. La Fama, Del. Tlalpan, 14269, Mexico City, Mexico.
FAU - Calderon Gamez, Daniela
AU  - Calderon Gamez D
AD  - Laboratorio de Nutricion Experimental, Instituto Nacional de Pediatria, Av. 
      Insurgentes Sur 3700, Letra C, Col. Insurgentes Cuicuilco, Del. Coyoacan, 04530, 
      Mexico City, Mexico.
FAU - Paz Tres, Carlos
AU  - Paz Tres C
AD  - Laboratorio de Neurofisiologia, Instituto Nacional de Neurologia y Neurocirugia, 
      Av. Insurgentes Sur 3877, Col. La Fama, Del. Tlalpan, 14269, Mexico City, Mexico.
FAU - Carvajal Aguilera, Karla G
AU  - Carvajal Aguilera KG
AD  - Laboratorio de Nutricion Experimental, Instituto Nacional de Pediatria, Av. 
      Insurgentes Sur 3700, Letra C, Col. Insurgentes Cuicuilco, Del. Coyoacan, 04530, 
      Mexico City, Mexico.
FAU - Phillips Farfan, Bryan V
AU  - Phillips Farfan BV
AUID- ORCID: 0000-0001-6470-6860
AD  - Laboratorio de Nutricion Experimental, Instituto Nacional de Pediatria, Av. 
      Insurgentes Sur 3700, Letra C, Col. Insurgentes Cuicuilco, Del. Coyoacan, 04530, 
      Mexico City, Mexico. bvphillips@yahoo.com.
LA  - eng
GR  - NA/Instituto Nacional de Pediatria/
PT  - Journal Article
DEP - 20180821
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Anticonvulsants)
RN  - 0 (Enzyme Inhibitors)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Anticonvulsants/pharmacology
MH  - *Caloric Restriction
MH  - Combined Modality Therapy
MH  - Enzyme Inhibitors/therapeutic use
MH  - Epilepsy/*prevention & control
MH  - Male
MH  - Metformin/*therapeutic use
MH  - Obesity/complications/*therapy
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - Caloric restriction
OT  - Electrical kindling
OT  - Epilepsy
OT  - Metformin
OT  - mTOR signaling pathway
EDAT- 2018/08/23 06:00
MHDA- 2018/11/06 06:00
CRDT- 2018/08/23 06:00
PHST- 2018/04/09 00:00 [received]
PHST- 2018/08/07 00:00 [accepted]
PHST- 2018/08/23 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/08/23 06:00 [entrez]
AID - 10.1007/s10571-018-0611-8 [pii]
AID - 10.1007/s10571-018-0611-8 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2018 Oct;38(7):1425-1438. doi: 10.1007/s10571-018-0611-8. 
      Epub 2018 Aug 21.