title: Zinc chelation reduces hippocampal neurogenesis after pilocarpine-induced seizure.
abstract: Several studies have shown that epileptic seizures increase hippocampal neurogenesis in the adult. However, the mechanism underlying increased neurogenesis after seizures remains largely unknown. Neurogenesis occurs in the subgranular zone (SGZ) of the hippocampus in the adult brain, although an understanding of why it actively occurs in this region has remained elusive. A high level of vesicular zinc is localized in the presynaptic terminals of the SGZ. Previously, we demonstrated that a possible correlation may exist between synaptic zinc localization and high rates of neurogenesis in this area after hypoglycemia. Using a lithium-pilocarpine model, we tested our hypothesis that zinc plays a key role in modulating hippocampal neurogenesis after seizure. Then, we injected the zinc chelator, clioquinol (CQ, 30 mg/kg), into the intraperitoneal space to reduce brain zinc availability. Neuronal death was detected with Fluoro Jade-B and NeuN staining to determine whether CQ has neuroprotective effects after seizure. The total number of degenerating and live neurons was similar in vehicle and in CQ treated rats at 1 week after seizure. Neurogenesis was evaluated using BrdU, Ki67 and doublecortin (DCX) immunostaining 1 week after seizure. The number of BrdU, Ki67 and DCX positive cell was increased after seizure. However, the number of BrdU, Ki67 and DCX positive cells was significantly decreased by CQ treatment. Intracellular zinc chelator, N,N,N0,N-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), also reduced seizure-induced neurogenesis in the hippocampus. The present study shows that zinc chelation does not prevent neurodegeneration but does reduce seizure-induced progenitor cell proliferation and neurogenesis. Therefore, this study suggests that zinc has an essential role for modulating hippocampal neurogenesis after seizure.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Bong Geom
authors.initials: BG
authors.lastname: Jang
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.forename: Lyo Min
authors.initials: LM
authors.lastname: Kwon
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.forename: Hong Ki
authors.initials: HK
authors.lastname: Song
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007464:Clioquinol / Q000008:administration & dosage / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects; D000089662:Doublecortin Protein; D005029:Ethylenediamines / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D010862:Pilocarpine / Q000009:adverse effects; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005029:Ethylenediamines; D018696:Neuroprotective Agents; D010862:Pilocarpine; D007464:Clioquinol; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine