PMID- 28902712
OWN - NLM
STAT- MEDLINE
DCOM- 20180523
LR  - 20211204
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 28
IP  - 15
DP  - 2017 Oct 18
TI  - Attenuation of pentylenetrazole-induced acute status epilepticus in rats by 
      adenosine involves inhibition of the mammalian target of rapamycin pathway.
PG  - 1016-1021
LID - 10.1097/WNR.0000000000000878 [doi]
AB  - Adenosine (ADO) has been characterized as an endogenous anticonvulsant and 
      alternative therapeutic drug, but its mechanism is not entirely clear. This study 
      aimed to examine the relationship of ADO with the mammalian target of rapamycin 
      (mTOR) in a Wistar rat model of pentylenetetrazole (PTZ)-induced acute status 
      epilepticus. ADO (200 mg/kg) was administered intraperitoneally 30 min before PTZ 
      (55-65 mg/kg) treatment, and Western blot assays and immunohistochemistry were 
      performed 3 h after the onset of acute status epilepticus to detect phospho-TOR 
      and the downstream target of mTOR, phospho-S6. The expression of these 
      phosphoproteins in the hippocampus was significantly increased in PTZ-treated 
      rats, but this increase was attenuated by the addition of ADO. To further verify 
      a role for ADO in attenuating mTOR activity, we also evaluated its ability to 
      suppress mTOR activity in normal rats that were not treated with PTZ. Our results 
      suggest that ADO suppresses mTOR and S6 phosphorylation in normal rats and that 
      this suppression can be reversed by the application of Compound C, an inhibitor 
      of AMP-activated protein kinase, which functions as an upstream suppressor of the 
      mTOR pathway. Thus, our results provide a novel antiepileptic mechanism for ADO 
      in suppressing mTOR pathway activation upon PTZ-induced acute status epilepticus.
FAU - Wang, Yuliang
AU  - Wang Y
AD  - aDepartment of Neurology, Qilu Hospital of Shandong University, Jinan bBinzhou 
      Medical University Hospital, Binzhou, Shandong, China.
FAU - Liu, Xuewu
AU  - Liu X
FAU - Wang, Yuan
AU  - Wang Y
FAU - Chen, Jinbo
AU  - Chen J
FAU - Han, Tao
AU  - Han T
FAU - Su, Lei
AU  - Su L
FAU - Zang, Kejun
AU  - Zang K
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Anticonvulsants)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - K72T3FS567 (Adenosine)
RN  - WM5Z385K7T (Pentylenetetrazole)
SB  - IM
MH  - Adenosine/*pharmacology
MH  - Adenylate Kinase/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Immunohistochemistry
MH  - Male
MH  - Pentylenetetrazole
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
MH  - Status Epilepticus/*drug therapy/*metabolism/pathology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2017/09/14 06:00
MHDA- 2018/05/24 06:00
CRDT- 2017/09/14 06:00
PHST- 2017/09/14 06:00 [pubmed]
PHST- 2018/05/24 06:00 [medline]
PHST- 2017/09/14 06:00 [entrez]
AID - 10.1097/WNR.0000000000000878 [doi]
PST - ppublish
SO  - Neuroreport. 2017 Oct 18;28(15):1016-1021. doi: 10.1097/WNR.0000000000000878.