title: Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis.
abstract: Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could accelerate this conversion. At low levels of KA, generating epileptiform activity without seizures, we indeed found increased rNSC activation and conversion into astrocytes. At high levels, generating sustained epileptic seizures, however, we find that rNSCs divide symmetrically and that both mother and daughter cells convert into reactive astrocytes. Our results demonstrate that a threshold response for neuronal hyperexcitation provokes a dramatic shift in rNSC function, which impairs adult hippocampal neurogenesis in the long term.
authors.affiliation: Achucarro Basque Center for Neuroscience, Laida Bidea 205, 48170 Zamudio, Spain; Ikerbasque Foundation, María Díaz de Haro 3, 6(th) Floor, 48013 Bilbao, Spain; University of the Basque Country (UPV/EHU), Barrio Sarrena s/n, 48940 Leioa, Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sierra
authors.affiliation: Achucarro Basque Center for Neuroscience, Laida Bidea 205, 48170 Zamudio, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: Martín-Suárez
authors.affiliation: Achucarro Basque Center for Neuroscience, Laida Bidea 205, 48170 Zamudio, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Valcárcel-Martín
authors.affiliation: Baylor College of Medicine, The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, 1250 Morsund Street, Houston, TX 77030, USA.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pascual-Brazo
authors.affiliation: KU Leuven, Oude Markt 13, 3000 Leuven, Belgium.
authors.forename: Sarah-Ann
authors.initials: SA
authors.lastname: Aelvoet
authors.affiliation: Achucarro Basque Center for Neuroscience, Laida Bidea 205, 48170 Zamudio, Spain.
authors.forename: Oihane
authors.initials: O
authors.lastname: Abiega
authors.affiliation: Baylor College of Medicine, The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, 1250 Morsund Street, Houston, TX 77030, USA.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Deudero
authors.affiliation: Baylor College of Medicine, The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, 1250 Morsund Street, Houston, TX 77030, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Brewster
authors.affiliation: University of the Basque Country (UPV/EHU), Barrio Sarrena s/n, 48940 Leioa, Spain.
authors.forename: Irantzu
authors.initials: I
authors.lastname: Bernales
authors.affiliation: Baylor College of Medicine, The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, 1250 Morsund Street, Houston, TX 77030, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Anderson
authors.affiliation: KU Leuven, Oude Markt 13, 3000 Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.affiliation: Baylor College of Medicine, The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, 1250 Morsund Street, Houston, TX 77030, USA. Electronic address: maletics@bcm.edu.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Maletić-Savatić
authors.affiliation: Achucarro Basque Center for Neuroscience, Laida Bidea 205, 48170 Zamudio, Spain; Ikerbasque Foundation, María Díaz de Haro 3, 6(th) Floor, 48013 Bilbao, Spain; University of the Basque Country (UPV/EHU), Barrio Sarrena s/n, 48940 Leioa, Spain. Electronic address: jm.encinas@ikerbasque.org.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Encinas
mesh_terms: D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007608:Kainic Acid / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D011595:Psychomotor Agitation / Q000503:physiopathology*
chemical_list: D007608:Kainic Acid