Abstract |
Inhibition of glycolytic metabolism may provide a new therapy for refractory epilepsy. Fructose-1,6-diphosphate ( FDP), which inhibits glycolysis and diverts glucose into the pentose phosphate pathway, has strong inhibitory action on seizures induced by chemical convulsants. Here, we investigated the effect of FDP on a rat model of rapid hippocampal kindling. After determining the after-discharge threshold (ADT), the seizure severity and after-discharge duration (ADD) were measured to study the antiepileptogenic effects of FDP (0.5 or 1.0 g/kg i.p. for 4 days). The mRNA expression levels of the brain-derived neurotrophic factor ( BDNF) and its principal receptor TrkB, which are key modulators of seizure activity, were determined in the ipsilateral hippocampus by real-time polymerase chain reaction (RT-PCR). High-dose FDP (1.0 g/kg) delayed kindling development together with shortened ADD, and high-dose treated rats also needed more kindling stimulations and more cumulative ADD to stage 4. However, it showed no significant antiepileptogenic effect at a lower dose of 0.5 g/kg. In addition, FDP attenuated BDNF and TrkB expression before and during kindling procedure; this result indicated that BDNF/TrkB signaling pathway may participate in the antiepileptogenic action of FDP. Our data demonstrates that FDP has a significant antiepileptogenic effect in kindling seizures and that it may be a potential antiepileptic drug in the future.
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Authors | Yao Ding, Shuang Wang, Man-man Zhang, Yi Guo, Yi Yang, Shu-qun Weng, Ji-min Wu, Xia Qiu, Mei-ping Ding |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 477
Issue 1
Pg. 33-6
(Jun 14 2010)
ISSN: 1872-7972 [Electronic] Ireland |
PMID | 20416358
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2010 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Brain-Derived Neurotrophic Factor
- Fructosediphosphates
- RNA, Messenger
- Receptor, trkB
- fructose-1,6-diphosphate
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Topics |
- Animals
- Brain-Derived Neurotrophic Factor
(biosynthesis, physiology)
- Fructosediphosphates
(metabolism, pharmacology)
- Kindling, Neurologic
- Male
- RNA, Messenger
(biosynthesis)
- Rats
- Rats, Sprague-Dawley
- Receptor, trkB
(biosynthesis, physiology)
- Seizures
(metabolism, physiopathology)
- Signal Transduction
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