Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.

<h4>Background</h4>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 induc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Vivian Capilla-Gonzalez, Sara Gil-Perotin, Antonio Ferragud, Luis Bonet-Ponce, Juan Jose Canales, Jose Manuel Garcia-Verdugo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d3976f7d46134159859faa733dc5e9ea
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d3976f7d46134159859faa733dc5e9ea
record_format	dspace
spelling	oai:doaj.org-article:d3976f7d46134159859faa733dc5e9ea2021-11-18T07:30:55ZExposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.1932-620310.1371/journal.pone.0029891https://doaj.org/article/d3976f7d46134159859faa733dc5e9ea2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22238669/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Vivian Capilla-GonzalezSara Gil-PerotinAntonio FerragudLuis Bonet-PonceJuan Jose CanalesJose Manuel Garcia-VerdugoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29891 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vivian Capilla-Gonzalez Sara Gil-Perotin Antonio Ferragud Luis Bonet-Ponce Juan Jose Canales Jose Manuel Garcia-Verdugo Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Vivian Capilla-Gonzalez Sara Gil-Perotin Antonio Ferragud Luis Bonet-Ponce Juan Jose Canales Jose Manuel Garcia-Verdugo
author_facet	Vivian Capilla-Gonzalez Sara Gil-Perotin Antonio Ferragud Luis Bonet-Ponce Juan Jose Canales Jose Manuel Garcia-Verdugo
author_sort	Vivian Capilla-Gonzalez
title	Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
title_short	Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
title_full	Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
title_fullStr	Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
title_full_unstemmed	Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
title_sort	exposure to n-ethyl-n-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d3976f7d46134159859faa733dc5e9ea
work_keys_str_mv	AT viviancapillagonzalez exposuretonethylnnitrosoureainadultmicealtersstructuralandfunctionalintegrityofneurogenicsites AT saragilperotin exposuretonethylnnitrosoureainadultmicealtersstructuralandfunctionalintegrityofneurogenicsites AT antonioferragud exposuretonethylnnitrosoureainadultmicealtersstructuralandfunctionalintegrityofneurogenicsites AT luisbonetponce exposuretonethylnnitrosoureainadultmicealtersstructuralandfunctionalintegrityofneurogenicsites AT juanjosecanales exposuretonethylnnitrosoureainadultmicealtersstructuralandfunctionalintegrityofneurogenicsites AT josemanuelgarciaverdugo exposuretonethylnnitrosoureainadultmicealtersstructuralandfunctionalintegrityofneurogenicsites
_version_	1718423378853888000

Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites.

Ejemplares similares