title: Persistent zinc depletion in the mossy fiber terminals in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy.
abstract: OBJECTIVE
  Zinc is released in synaptic vesicles with glutamate, and modulates glutamatergic neurotransmission. In brain, the highest amount of zinc, detected by Timm staining, is in the mossy fiber (MF) system in the hippocampus. In the intrahippocampal kainate (KA) mouse model of mesial temporal lobe epilepsy, which is elicited by intrahippocampal KA, prominent MF sprouting develops rapidly within 2 weeks post-KA. However, the intensity of Timm staining is reduced gradually thereafter. The present study is designed to determine the mechanisms underlying this reduction of Timm staining.
  
  
  METHODS
  The changes in Timm staining, and VGluT1, Synapsin-1, and zinc transporter 3 (ZnT3) immunoreactivity (IR) were examined from 4-56 days post-KA. An analysis of glutamate release in the KA-injected hippocampus was conducted by microdialysis before and during the continuous injection of midazolam (MDZ).
  
  
  RESULTS
  At 56 days post-KA, Timm staining disappeared completely, whereas VGluT-1-, Synapsin-1-, and ZnT3-IR were increased in the sprouted MF boutons. However, when the seizures were suppressed by a continuous perfusion of MDZ, the glutamate release in the hippocampus decreased and Timm staining was recovered.
  
  
  CONCLUSIONS
  This study showed that the reduction of Timm staining is the result of decreased zinc content but not the loss of MF itself. The reduction is the result of the enhanced release of zinc relative to storage, and it should facilitate the glutamate excitation that might be related to the epileptogenesis and rapid advancement of the morphologic changes in this model.
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Nagaizumi, Shizuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mitsuya
authors.forename: Naoki
authors.initials: N
authors.lastname: Nitta
authors.forename: Fumio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis / Q000379:methods; D008874:Midazolam / Q000494:pharmacology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D015032:Zinc / Q000172:deficiency*
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D006993:Hypnotics and Sedatives; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C493465:Slc17a7 protein, mouse; C491177:Slc30a3 protein, mouse; D016704:Synapsins; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid; D015032:Zinc; D008874:Midazolam; D007608:Kainic Acid