[Correlation between hippocampal mossy fiber sprouting and synaptic reorganization and mechanisms of temporal lobe epilepsy].
OBJECTIVE
To explore the effects of the ultrastructural features of sprouted mossy fiber synapses in the mechanism of temporal lobe epilepsy. To explore the correlation between axon guidance molecule-netrin-1 gene expression and mossy fiber synaptic reorganization.


METHODS
Sixty-one SD rats underwent intraperitoneal injection of lithium chloride and pilocarpine to establish models of status epilepticus characterized with temporal lobe epilepsy. Nineteen rats were used as controls. One, 2, and 4 weeks after the injection, a certain numbers of rat were killed with their brains taken out. The sprouted mossy fiber synaptic terminals were labeled by Timm histochemistry and the ultrastructure of new synapses were observed by electron microscopy. By in situ hybridization, the mRNA expression of netrin-1 gene was observed.


RESULTS
The sprouted mossy fiber synapses in epileptic rats most commonly formed asymmetric synapses with dendritic spines and occasionally with granule cell somata. Seven days after the injection, up-regulation of netrin-1 mRNA expression was seen in the dentate granule cell layers of hippocampus and continued to 4 weeks after the injection. The time course of the increase of netrin-1 mRNA in the dentate granule cell layers was correlated with the time course of mossy fiber sprouting and synaptic reorganization in hippocampus.


CONCLUSIONS
The ultrastructural features of sprouted mossy fiber synapses support the viewpoint that the reorganization of synapses prominently involves the formation of recurrent excitatory circuits. The axon guidance molecule- netrin-1 plays an important role in the process of mossy fiber axonal outgrowth and synaptogenesis in the hippocampal dentate gyrus.
Lin
Hua
H
Department of Neurology, Peking Union Medical College Hospital, Beijing 100730, China.
Wu
Li-wen
LW
Huang
Yuan-gui
YG
Chen
Yun-chun
YC
Wen
Xiao-ni
XN
D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000473:pathology*; D017403:In Situ Hybridization; D018021:Lithium Chloride; D008297:Male; D008854:Microscopy, Electron; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000235:genetics; D000075388:Netrin-1; D010862:Pilocarpine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000235:genetics
D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010862:Pilocarpine; D000075388:Netrin-1; D018021:Lithium Chloride