title: Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus.
abstract: Emerging evidence has linked chronic temporal lobe epilepsy to dramatically reduced neurogenesis in the dentate gyrus. However, the profile of different components of neurogenesis in the chronically epileptic hippocampus is still unclear, especially the incorporation of newly generated cells. To address the issue, newly generated cells in the sub-granular zone of the dentate gyrus were labeled by the proliferation marker bromodeoxyuridine (BrdU) or retroviral vector expressing green fluorescent protein 2 months after pilocarpine-induced status epilepticus. The newly generated neurons that extended axons to CA3 area or integrated into memory circuits were visualized by cholera toxin B subunit retrograde tracing, and detecting activation of BrdU(+) cells following a recall of spatial memory test at the chronic stage of TLE. We found that the microenvironment was still able to sustain significant neuronal differentiation of newly generated cells at 2 months post-status epilepticus time-point, and newly added neurons into granular cell layer were still able to integrate into neuronal circuitry, both anatomically and functionally. Quantified analyses of BrdU(+) or Ki-67(+) cells demonstrated that there was a reduced proliferation of progenitor cells and diminished survival of newly generated cells in the epileptic hippocampus. Both decreased levels of neurotrophic factors in the surrounding milieu and cell loss in the CA3 area might contribute the decreased production of new cells and their survival following chronic epilepsy. These results suggest that decreased neurogenesis in the chronically epileptic hippocampus 2 months post status epilepticus is not associated with altered integration of newly generated neurons, and that developing strategies to augment hippocampal neurogenesis in chronic epilepsy might be protective.
authors.affiliation: Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061; Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061.
authors.forename: Xin-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Biomedical Laboratory for Medical Students, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061.
authors.forename: Yao-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061.
authors.forename: Jian-Shui
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061.
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Xiao
authors.affiliation: Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061. Electronic address: liujianxin@mail.xjtu.edu.cn.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Liu
authors.affiliation: Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, China 710061. Electronic address: Liuy5599@mail.xjtu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018721:Muscarinic Agonists; D009415:Nerve Net / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010862:Pilocarpine / Q000633:toxicity; D012190:Retroviridae / Q000235:genetics; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*; D013234:Stem Cells; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D010862:Pilocarpine; D002772:Cholera Toxin
keywords: Epilepsy; Hippocampus; Neurogenesis; Subgranular zone