title: Zinc plus cyclo-(His-Pro) promotes hippocampal neurogenesis in rats.
abstract: Zinc is a central actor in regulating stem cell proliferation and neurogenesis in the adult brain. High levels of vesicular zinc are found in the presynaptic terminals. It has been demonstrated that high levels of vesicular zinc are localized in the presynaptic terminals of the granule cells of the dentate gyrus (DG) and that neurogenesis occurs in the subgranular zone (SGZ). Furthermore, zinc chelation reduces hippocampal neurogenesis in pathological conditions such as hypoglycemia, epilepsy and traumatic brain injury. Here we test the effects of zinc plus cyclo-(His-Pro) (CHP) treatment on neurogenesis in the adult SGZ. In order to increase brain zinc, Sprague-Dawley (SD) rats, aged 5weeks, were given zinc plus CHP (ZC, 27mg/kg) orally available once per day for 2weeks. BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 1week after initial ZC treatment. Neurogenesis was analyzed by BrdU, Ki67 and doublecortin (DCX) immunostaining. The number of progenitor cells and immature neurons were significantly increased in the DG following 2weeks of ZC treatment. Hippocampal vesicular zinc content was evaluated with TSQ staining. Vesicular TSQ fluorescent intensity was seen to increase in the mossy fiber area at 2weeks after ZC treatment. The present study demonstrates that zinc supplementation by ZC treatment increases hippocampal neurogenesis and levels of vesicular zinc. These findings provide evidence in support of the essential role of zinc in modulating hippocampal neurogenesis.
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors: Bo Young
authors: BY
authors: Choi
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors: In Yeol
authors: IY
authors: Kim
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors: Jin Hee
authors: JH
authors: Kim
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors: Bo Eun
authors: BE
authors: Lee
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors: Song Hee
authors: SH
authors: Lee
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors: A Ra
authors: AR
authors: Kho
authors: Inha University, Department of Nursing, Incheon, Republic of Korea.
authors: Min
authors: M
authors: Sohn
authors: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea. Electronic address: swsuh@hallym.ac.kr.
authors: Sang Won
authors: SW
authors: Suh
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002491:Central Nervous System Agents; C000714848:Dcx protein, rat; D004151:Dipeptides; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; C035699:histidylproline; D001973:Bromodeoxyuridine; D015032:Zinc
keywords: hippocampus; neurogenesis; zinc; zinc plus cyclo-(His-Pro)