title: Hippocampal CA field neurogenesis after pilocarpine insult: The hippocampal fissure as a neurogenic niche.
abstract: Pilocarpine model for temporal lobe epilepsy has shown aberrant neurogenesis, but mainly restricted to the dentate gyrus (DG). Herein, by using a modified protocol, combining pilocarpine with ipratropium bromide, we unexpectedly observed a heretofore-unrecognized distinct cellular population expressing the neuroprogenitor marker doublecortin (DCX) on post insult days (PID) 10, 14 and 18, mainly located in the temporal segment of the hippocampal fissure (hf). Some of these DCX+ cells possessed high morphological complexity and seemed to disperse toward the CA fields. Next, we injected bromodeoxyuridine (BrdU) in early (PID 2-4) and delayed (PID 5-7) fashions and killed the rats 7-35 days later for immunohistochemical and anatomical analysis. Massive increase of BrdU labeling was found in the delayed group and the neural stem cell-specific marker nestin was highly expressed in the same narrow band on PID7, so was glial fibrillary acidic protein (GFAP). Using double labeling with BrdU and a mature neuron marker NeuN, we found discrete but clear BrdU+/NeuN+ double labeled cells in the Cornu Ammonis (CA) pyramidal cell layer on PID35. Based on immunohistochemical and anatomical observations, as well as time-course analysis of BrdU, nestin, GFAP, DCX and NeuN expressions in this population of cells located in/near hf, we wish to suggest that this structure harbors neurogenic niches, in addition of the possible dispersion of neuroprogenitors from subgranular niches to CA fields also revealed by this study. Our results support the few previous reports demonstrating hippocampal CA field neurogenesis in adult rats. Mechanistic basis of the phenomenon is discussed.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico. Electronic address: limei@unam.mx.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
authors.forename: Vito S
authors.initials: VS
authors.lastname: Hernández
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
authors.forename: Felipe S
authors.initials: FS
authors.lastname: Estrada
authors.affiliation: Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, 02006 Albacete, Spain. Electronic address: Rafael.Lujan@uclm.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
mesh_terms: D000818:Animals; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D055153:Stem Cell Niche
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018721:Muscarinic Agonists; D010862:Pilocarpine
keywords: 5-Bromo-2′-deoxyuridine (BrdU); Glial fibrillary acidic protein (GFAP), doublecortin (DCX); Ipratropium bromide; Nestin; Neuronal specific nuclear protein (NeuN)