Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats

Detalhes bibliográficos
Autor(a) principal: Lima, A.
Data de Publicação: 2014
Outros Autores: Sardinha, Vanessa Morais, Oliveira, A. F., Reis, M., Mota, Cristina de Fátima Sousa da, Silva, M. A., Marques, Fernanda, Cerqueira, João, Pinto, Luisa, Sousa, Nuno, Oliveira, João F.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/32922
Resumo: Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-a-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.
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spelling Astrocyte pathology in the prefrontal cortex impairs the cognitive function of ratsAminoadipateAstrocyteCognitionLearningPrefrontal cortexScience & TechnologyInterest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-a-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.This work was supported by the Marie Curie Fellowship FP7-PEOPLE-2010-IEF 273936, BIAL Foundation Grants 138/2008 and 61/2010, FEDER funds through Operational program for competitiveness factors-COMPETE -, ON2 Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN/FEDER, and by national funds through FCT-Foundation for Science and Technology-project (PTDC/SAU-NSC/118194/2010) and fellowships (SFRH/BPD/66151/2009 and SFRH/BD/89714/2012).Palgrave MacmillanUniversidade do MinhoLima, A.Sardinha, Vanessa MoraisOliveira, A. F.Reis, M.Mota, Cristina de Fátima Sousa daSilva, M. A.Marques, FernandaCerqueira, JoãoPinto, LuisaSousa, NunoOliveira, João F.20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/32922eng1359-418410.1038/mp.2013.18224419043www.nature.cominfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:35:37Zoai:repositorium.sdum.uminho.pt:1822/32922Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:31:29.729958Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
title Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
spellingShingle Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
Lima, A.
Aminoadipate
Astrocyte
Cognition
Learning
Prefrontal cortex
Science & Technology
title_short Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
title_full Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
title_fullStr Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
title_full_unstemmed Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
title_sort Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
author Lima, A.
author_facet Lima, A.
Sardinha, Vanessa Morais
Oliveira, A. F.
Reis, M.
Mota, Cristina de Fátima Sousa da
Silva, M. A.
Marques, Fernanda
Cerqueira, João
Pinto, Luisa
Sousa, Nuno
Oliveira, João F.
author_role author
author2 Sardinha, Vanessa Morais
Oliveira, A. F.
Reis, M.
Mota, Cristina de Fátima Sousa da
Silva, M. A.
Marques, Fernanda
Cerqueira, João
Pinto, Luisa
Sousa, Nuno
Oliveira, João F.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Lima, A.
Sardinha, Vanessa Morais
Oliveira, A. F.
Reis, M.
Mota, Cristina de Fátima Sousa da
Silva, M. A.
Marques, Fernanda
Cerqueira, João
Pinto, Luisa
Sousa, Nuno
Oliveira, João F.
dc.subject.por.fl_str_mv Aminoadipate
Astrocyte
Cognition
Learning
Prefrontal cortex
Science & Technology
topic Aminoadipate
Astrocyte
Cognition
Learning
Prefrontal cortex
Science & Technology
description Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-a-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/32922
url http://hdl.handle.net/1822/32922
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1359-4184
10.1038/mp.2013.182
24419043
www.nature.com
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Palgrave Macmillan
publisher.none.fl_str_mv Palgrave Macmillan
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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