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Exposure to N-Ethyl-N-Nitrosourea in adult mice alters structural and functional integrity of neurogenic sites


Capilla-Gonzalez, V and Gil-Perotin, S and Ferraqud, A and Bonet-Ponce, L and Canales, JJ and Garcia-Verdugo, JM, Exposure to N-Ethyl-N-Nitrosourea in adult mice alters structural and functional integrity of neurogenic sites, PloS one, 7, (1) Article e29891. ISSN 1932-6203 (2012) [Refereed Article]


Copyright Statement

Copyright 2012 Capilla-Gonzalez et al. Licenced under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1371/journal.pone.0029891


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.

Methodology/Principal Findings: 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/Significance: 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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in psychology
UTAS Author:Canales, JJ (Professor Juan Canales)
ID Code:121294
Year Published:2012
Web of Science® Times Cited:22
Deposited By:Psychology
Deposited On:2017-09-21
Last Modified:2017-10-02
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