PMID- 26684398
OWN - NLM
STAT- MEDLINE
DCOM- 20161102
LR  - 20161230
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 27
IP  - 4
DP  - 2016 Mar 2
TI  - A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive 
      astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.
PG  - 213-9
LID - 10.1097/WNR.0000000000000511 [doi]
AB  - The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is 
      difficult to establish. In this study, we investigated the effect of a single 
      sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of 
      seizures that were subsequently induced by daily electrical stimulation 
      (kindling) of the amygdaloid formation. Male Sprague-Dawley rats were each 
      implanted with an electrode in the right basolateral amygdala and an indwelling 
      cannula in the right ventricle. The animals were randomized into groups and were 
      administered one of the following treatments: saline, PILO, 
      saline+L-alpha-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or 
      PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and 
      electroencephalography were performed once daily. We performed 
      immunohistochemistry and western blot for glial fibrillary acidic protein and 
      glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete 
      brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced 
      the progression of amygdaloid-kindling seizures and was accompanied by an 
      increase in reactive-astrocyte and GS (content and activity) in the hippocampus 
      and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic 
      and GS function, respectively, abolished the effect of PILO on 
      amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a 
      proconvulsant may enhance the progression of subsequent epilepsy and astrocytic 
      GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could 
      be inhibition of astrocytes and/or GS.
FAU - Sun, Hong-Liu
AU  - Sun HL
AD  - aSchool of Pharmaceutical Sciences, Binzhou Medical University, Yantai bInstitute 
      of Radiation Medicine, Shandong Academy of Medical Sciences, Jinan, China.
FAU - Deng, Da-Ping
AU  - Deng DP
FAU - Pan, Xiao-Hong
AU  - Pan XH
FAU - Wang, Chao-Yun
AU  - Wang CY
FAU - Zhang, Xiu-Li
AU  - Zhang XL
FAU - Chen, Xiang-Ming
AU  - Chen XM
FAU - Wang, Chun-Hua
AU  - Wang CH
FAU - Liu, Yu-Xia
AU  - Liu YX
FAU - Li, Shu-Cui
AU  - Li SC
FAU - Bai, Xian-Yong
AU  - Bai XY
FAU - Zhu, Wei
AU  - Zhu W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Muscarinic Agonists)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 1982-67-8 (Methionine Sulfoximine)
RN  - 1K7B1OED4N (2-Aminoadipic Acid)
RN  - EC 6.3.1.2 (Glutamate-Ammonia Ligase)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - 2-Aminoadipic Acid/pharmacology
MH  - Animals
MH  - Astrocytes/*drug effects/enzymology
MH  - Basolateral Nuclear Complex/*drug effects/enzymology
MH  - Catheters, Indwelling
MH  - Disease Models, Animal
MH  - Electric Stimulation
MH  - Electrodes, Implanted
MH  - Fluorescent Antibody Technique
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Glutamate-Ammonia Ligase/*metabolism
MH  - Hippocampus/drug effects/enzymology
MH  - Kindling, Neurologic/*drug effects/metabolism
MH  - Lithium Chloride
MH  - Male
MH  - Methionine Sulfoximine/pharmacology
MH  - Muscarinic Agonists/*toxicity
MH  - Pilocarpine/*toxicity
MH  - Rats, Sprague-Dawley
MH  - Temporal Lobe/drug effects/enzymology
EDAT- 2015/12/20 06:00
MHDA- 2016/11/03 06:00
CRDT- 2015/12/20 06:00
PHST- 2015/12/20 06:00 [entrez]
PHST- 2015/12/20 06:00 [pubmed]
PHST- 2016/11/03 06:00 [medline]
AID - 10.1097/WNR.0000000000000511 [doi]
PST - ppublish
SO  - Neuroreport. 2016 Mar 2;27(4):213-9. doi: 10.1097/WNR.0000000000000511.