title: Loss of input from the mossy cells blocks maturation of newly generated granule cells.
abstract: The objective of this work is to check whether the input from the mossy cells to the inner molecular layer is necessary for the integration and maturation of the newly generated granule cells of the dentate gyrus (DG) in mice, and if after status epilepticus the sprouting of the mossy fibers can substitute for this projection. Newly generated cells were labeled by administration of 5-bromo-deoxyuridine either before or after pilocarpine administration. The neuronal loss in the hippocampus after administration of pilocarpine combined with scopolamine and diazepam seemed restricted to the hilar mossy cells. The maturation of the granule cells was studied using immunohistochemistry for calretinin and NeuN in combination with detection of 5-bromo-deoxyuridine. The sprouting of the mossy fibers was detected using Timm staining for zinc-rich boutons. In normal conditions, granule cells took about 2 weeks to lose the immature marker calretinin. After the loss of the mossy cells, newly generated granule cells remained expressing calretinin for more than a month, until the sprouting of the mossy fibers substituted for the projection of the mossy cells in the inner molecular layer of the DG. Therefore, a proper pattern of connectivity is necessary for the normal development and integration of newly generated granule cells in the adult brain. In a changed environment they cannot adapt transforming in other cell types; simply they are unable to mature. The sprouting of the mossy fibers, although aberrant and a probable source of epileptic activity, may be important for the correct physiology of the granule cells, restoring a likeness of normality in their connective environment. The survival of granule cells incorporated as mature neurons was increased after pilocarpine when compared with normal conditions. Thus, it is likely that the reorganization of the circuitry after the loss of the mossy cells facilitates the survival and incorporation of the newly generated granule cells.
authors: Departamento de Biología Celular, Unidad de Neurobiología, Facultad de Ciencias Biológicas, Universidad de Valencia, E-46.100 Burjasot, Spain.
authors: Ana-Isabel
authors: AI
authors: Marqués-Marí
authors: Juan
authors: J
authors: Nacher
authors: Carlos
authors: C
authors: Crespo
authors: María
authors: M
authors: Gutièrrez-Mecinas
authors: Francisco-José
authors: FJ
authors: Martínez-Guijarro
authors: José-Miguel
authors: JM
authors: Blasco-Ibáñez
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D015415:Biomarkers; D001973:Bromodeoxyuridine; D064032:Calbindin 2; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003292:Convulsants; D004268:DNA-Binding Proteins; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D003975:Diazepam; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism* / Q000648:ultrastructure; D018727:Muscarinic Antagonists; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D010862:Pilocarpine; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012601:Scopolamine; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D003292:Convulsants; D004268:DNA-Binding Proteins; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D064030:S100 Calcium Binding Protein G; D010862:Pilocarpine; D012601:Scopolamine; D001973:Bromodeoxyuridine; D003975:Diazepam