title: Status epilepticus alters neurogenesis and decreases the number of GABAergic neurons in the septal dentate gyrus of 9-day-old rats at the early phase of epileptogenesis.
abstract: The effects of a prolonged seizure, i.e. status epilepticus (SE), on neurogenesis of dentate granule cells (DGCs) in the immature dentate gyrus (DG) and possible changes in the phenotypes of the newborn neurons have remained incompletely characterized. We have now studied neurogenesis of DGCs in 9-day-old (postnatal, P9) rats 1 week after kainate (KA)-induced SE using 5-bromo-2-deoxyuridine (BrdU) immunostaining. The phenotype characterization of the newborn cells was carried out by immunofluorescence double labeling using doublecortin (DCX) and nestin as markers for immature cells, and glial fibrillary acid protein (GFAP) as a marker for glial cells. Newborn GABAergic neurons were further identified with antibodies for parvalbumin, glutamate decarboxylase 67 (GAD67), and the GABAA receptor α1 subunit, and mRNA expression of GABAergic and immature neurons was measured with quantitative real-time PCR (qPCR) in the DG. Our results show that the number of newborn as well as GABAergic neurons was significantly decreased after SE in the superior blade of the septal DG. The majority of the newborn BrdU-stained neurons co-expressed DCX, but neither nestin nor GFAP. In both experimental groups, newborn neurons were frequently localized in close contact, but not co-localized, with the cells positively stained for the GABAergic cell markers. Nestin and calretinin mRNA expression were significantly increased after SE. Our results suggest that SE-induced disruption of DGC neurogenesis and decreased number of GABAergic neurons could modify the connectivity between these cells and disturb the maturation of the GABAergic neurotransmission in the immature DG at the early epileptogenic phase.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Itäinen Pitkäkatu 4 B, 20014 University of Turku, Finland.
authors.forename: H B
authors.initials: HB
authors.lastname: Laurén
authors.forename: S
authors.initials: S
authors.lastname: Ruohonen
authors.forename: T-K
authors.initials: TK
authors.lastname: Kukko-Lukjanov
authors.forename: J E
authors.initials: JE
authors.lastname: Virta
authors.forename: M
authors.initials: M
authors.lastname: Grönman
authors.forename: F R
authors.initials: FR
authors.lastname: Lopez-Picon
authors.forename: J T
authors.initials: JT
authors.lastname: Järvelä
authors.forename: I E
authors.initials: IE
authors.lastname: Holopainen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D059330:GABAergic Neurons / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D011963:Receptors, GABA-A; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D001973:Bromodeoxyuridine; D007608:Kainic Acid