title: Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
abstract: BACKGROUND
  Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis.
  
  
  RESULTS
  2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively.
  
  
  CONCLUSIONS
  The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits.
authors.affiliation: Laboratorio de Neurobiologia Comparada, Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, Universidad de Valencia, Valencia, Spain. vivian.capilla@uv.es
authors.forename: Vivian
authors.initials: V
authors.lastname: Capilla-Gonzalez
authors.forename: Sara
authors.initials: S
authors.lastname: Gil-Perotin
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferragud
authors.forename: Luis
authors.initials: L
authors.lastname: Bonet-Ponce
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Canales
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D004781:Environmental Exposure; D005038:Ethylnitrosourea / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure*; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology
chemical_list: D000477:Alkylating Agents; D005038:Ethylnitrosourea