title: Zinc chelation reduces traumatic brain injury-induced neurogenesis in the subgranular zone of the hippocampal dentate gyrus.
abstract: Numerous studies have demonstrated that traumatic brain injury (TBI) increases hippocampal neurogenesis in the rodent brain. However, the mechanisms underlying increased neurogenesis after TBI remain unknown. Continuous neurogenesis occurs in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) in the adult brain. The mechanism that maintains active neurogenesis in the hippocampal area is not known. A high level of vesicular zinc is localized in the presynaptic terminals of the SGZ (mossy fiber). The mossy fiber of dentate granular cells contains high levels of chelatable zinc in their terminal vesicles, which can be released into the extracellular space during neuronal activity. Previously, our lab presented findings indicating that a possible correlation may exist between synaptic zinc localization and high rates of neurogenesis in this area after hypoglycemia or epilepsy. Using a weight drop animal model to mimic human TBI, we tested our hypothesis that zinc plays a key role in modulating hippocampal neurogenesis after TBI. Thus, we injected a zinc chelator, clioquinol (CQ, 30mg/kg), into the intraperitoneal space to reduce brain zinc availability twice per day for 1 week. Neuronal death was evaluated with Fluoro Jade-B and NeuN staining to determine whether CQ has neuroprotective effects after TBI. The number of degenerating neurons (FJB (+)) and live neurons (NeuN (+)) was similar in vehicle and in CQ-treated rats at 1 week after TBI. Neurogenesis was evaluated using BrdU, Ki67 and doublecortin (DCX) immunostaining 1 week after TBI. The number of BrdU, Ki67 and DCX positive cell was increased after TBI. However, the number of BrdU, Ki67 and DCX positive cells was significantly decreased by CQ treatment. The present study shows that zinc chelation did not prevent neurodegeneration but did reduce TBI-induced progenitor cell proliferation and neurogenesis. Therefore, this study suggests that zinc has an essential role for modulating hippocampal neurogenesis after TBI.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: In Yeol
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Inha University, Department of Nursing, Incheon, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea. Electronic address: swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology*; D007464:Clioquinol / Q000627:therapeutic use*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism*; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000378:metabolism
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D007464:Clioquinol; D015032:Zinc
keywords: Clioquinol; Hippocampus; Neurogenesis; Traumatic brain injury; Zinc