Fructose-1,6-diphosphate inhibits seizure acquisition in fast hippocampal kindling.
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.
Ding
Yao
Y
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
Wang
Shuang
S
Zhang
Man-man
MM
Guo
Yi
Y
Yang
Yi
Y
Weng
Shu-qun
SQ
Wu
Ji-min
JM
Qiu
Xia
X
Ding
Mei-ping
MP
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000502:physiology; D005635:Fructosediphosphates / Q000378:metabolism / Q000494:pharmacology*; D007696:Kindling, Neurologic; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000096:biosynthesis / Q000502:physiology; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction
D019208:Brain-Derived Neurotrophic Factor; D005635:Fructosediphosphates; D012333:RNA, Messenger; D020813:Receptor, trkB; C029063:fructose-1,6-diphosphate