[Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5 expression in kainic acid induced rat model of epilepsy].
OBJECTIVE
Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. The aim of the study was to reveal the possible mechanism from the view points of synaptic reorganization and GluR(5) expression in hippocampus.


METHODS
Epilepsy was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all control animals were fed with normal rodent chow, whereas experimental rats were fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were recorded. Mossy fiber sprouting and neuron damage in hippocampus were investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus.


RESULTS
KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly higher in KA induced animals than that in saline control animals but it was similar in different diet fed groups. No significant differences were found in the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus, CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg pro] had significantly higher GluR(5) expression in hippocampus than control diet-fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same.


CONCLUSIONS
Mossy fiber sprouting may be responsible for epileptogenesis in KA induced model and KD can suppress seizures in these animals. KD may upregulate young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased inhibition to prevent the propagation of seizure.
Xu
Xiang-ping
XP
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, China.
Sun
Ruo-peng
RP
Jin
Rui-feng
RF
D000818:Animals; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D023902:Chromosome Pairing / Q000187:drug effects*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D055423:Diet, Ketogenic / Q000379:methods; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007608:Kainic Acid; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D012333:RNA, Messenger; D018092:Kainic Acid Receptors