Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
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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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 |
repository.mail.fl_str_mv |
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1799132824082579456 |