Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/4242 |
Resumo: | Most animal model studies of autism spectrum disorder (ASD) have been performed in males, which may be a reflex of the 3-times higher prevalence in boys than in girls. For this reason, little is known about the mechanisms underlying disease progression in females, and nothing is known about potential associations between microglial changes in the lateral septum (LS) and adult female cognition. Prenatal exposure to valproic acid (VPA) in mice has been widely used as an experimental model of autism-like behaviors associated with cellular changes. However, no study has reported the influence of VPA exposure in utero and its consequences on limbic system-dependent tasks or the microglial response in the LS in adult female mice. We compared the exploratory activity and risk assessment in novel environments of BALB/c control mice to mice exposed in utero to VPA and estimated the total number of microglia in the LS using an optical fractionator. On day 12.5 of pregnancy, females received diluted VPA or saline by gavage. After weaning, VPA exposed or control pups were separately housed in standard laboratory cages. At 5 months of age, all mice underwent behavioral testing and their brain sections were immunolabelled using IBA-1 antibody. In the open field test, VPA group showed a greater distance traveled, which was accompanied by less immobility, less time spent on the periphery and a greater number, crossed lines. Similar findings were found in the elevated plus maze test, where VPA mice traveled greater distances, immobility was significantly higher than that of control and VPA group spent less time on the closed arms of apparatus. Stereological analysis demonstrated higher microglial total number and density in the LS of VPA mice, as the cell count was greater, but the volume was similar. Therefore, we suggest that an increase in microglia in the LS may be part of the cellular changes associated with behavioral dysfunction in the VPA model of ASD. |
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Leão, Ellen Rose Leandro Ponce deSouza, Dilza Nazaré Colares deMoura, Larissa Victória Barra deSilveira Júnior, Antonio Morais daSantos, Alinne Lorrany Gomes dosDiniz, Daniel GuerreiroDiniz, Cristovam Wanderley PicançoSosthenes, Marcia Consentino Kronka2021-02-03T20:23:56Z2021-02-03T20:23:56Z2021LEÃO, Ellen Rose Leandro Ponce de et al. Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period. Journal of Chemical Neuroanatomy, v. 111, n. xx, p. xx, Jan. 2021.0891-0618https://patua.iec.gov.br/handle/iec/424210.1016/j.jchemneu.2020.101875Most animal model studies of autism spectrum disorder (ASD) have been performed in males, which may be a reflex of the 3-times higher prevalence in boys than in girls. For this reason, little is known about the mechanisms underlying disease progression in females, and nothing is known about potential associations between microglial changes in the lateral septum (LS) and adult female cognition. Prenatal exposure to valproic acid (VPA) in mice has been widely used as an experimental model of autism-like behaviors associated with cellular changes. However, no study has reported the influence of VPA exposure in utero and its consequences on limbic system-dependent tasks or the microglial response in the LS in adult female mice. We compared the exploratory activity and risk assessment in novel environments of BALB/c control mice to mice exposed in utero to VPA and estimated the total number of microglia in the LS using an optical fractionator. On day 12.5 of pregnancy, females received diluted VPA or saline by gavage. After weaning, VPA exposed or control pups were separately housed in standard laboratory cages. At 5 months of age, all mice underwent behavioral testing and their brain sections were immunolabelled using IBA-1 antibody. In the open field test, VPA group showed a greater distance traveled, which was accompanied by less immobility, less time spent on the periphery and a greater number, crossed lines. Similar findings were found in the elevated plus maze test, where VPA mice traveled greater distances, immobility was significantly higher than that of control and VPA group spent less time on the closed arms of apparatus. Stereological analysis demonstrated higher microglial total number and density in the LS of VPA mice, as the cell count was greater, but the volume was similar. Therefore, we suggest that an increase in microglia in the LS may be part of the cellular changes associated with behavioral dysfunction in the VPA model of ASD.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Microscopia Eletrônica. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Hospital Universitário João de Barros Barreto. Laboratório de Investigações em Neurodegeneração e Infecção. Belém, PA, Brazil.engElsevierLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal periodinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleTranstorno Autístico / genéticaÁcido Valproico / análiseMicroglia / citologiaDoenças do Sistema Nervoso / genéticaCartilagens Nasaisinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period.pdfLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period.pdfapplication/pdf551083https://patua.iec.gov.br/bitstreams/572087d4-8d8b-4cc3-ad61-75d2c3cd5117/downloadc9a9c128e29cac82a5d7fdf3f4e6da73MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/24761f51-cd98-4174-a424-ef6abf6de94e/download11832eea31b16df8613079d742d61793MD52TEXTLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period.pdf.txtLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period.pdf.txtExtracted texttext/plain2https://patua.iec.gov.br/bitstreams/666f0e86-8361-4e87-a57a-6a9641a35934/downloade1c06d85ae7b8b032bef47e42e4c08f9MD55THUMBNAILLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period.pdf.jpgLateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period.pdf.jpgGenerated Thumbnailimage/jpeg3095https://patua.iec.gov.br/bitstreams/2e21479b-657b-4645-b082-6e0710ed55fb/download71859d578212107f7f8c49a4ce09d9eeMD56iec/42422022-10-20 22:46:30.576oai:patua.iec.gov.br:iec/4242https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T22:46:30Repositório Digital do Instituto Evandro Chagas (Patuá) - 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dc.title.pt_BR.fl_str_mv |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
title |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
spellingShingle |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period Leão, Ellen Rose Leandro Ponce de Transtorno Autístico / genética Ácido Valproico / análise Microglia / citologia Doenças do Sistema Nervoso / genética Cartilagens Nasais |
title_short |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
title_full |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
title_fullStr |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
title_full_unstemmed |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
title_sort |
Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period |
author |
Leão, Ellen Rose Leandro Ponce de |
author_facet |
Leão, Ellen Rose Leandro Ponce de Souza, Dilza Nazaré Colares de Moura, Larissa Victória Barra de Silveira Júnior, Antonio Morais da Santos, Alinne Lorrany Gomes dos Diniz, Daniel Guerreiro Diniz, Cristovam Wanderley Picanço Sosthenes, Marcia Consentino Kronka |
author_role |
author |
author2 |
Souza, Dilza Nazaré Colares de Moura, Larissa Victória Barra de Silveira Júnior, Antonio Morais da Santos, Alinne Lorrany Gomes dos Diniz, Daniel Guerreiro Diniz, Cristovam Wanderley Picanço Sosthenes, Marcia Consentino Kronka |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Leão, Ellen Rose Leandro Ponce de Souza, Dilza Nazaré Colares de Moura, Larissa Victória Barra de Silveira Júnior, Antonio Morais da Santos, Alinne Lorrany Gomes dos Diniz, Daniel Guerreiro Diniz, Cristovam Wanderley Picanço Sosthenes, Marcia Consentino Kronka |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Transtorno Autístico / genética Ácido Valproico / análise Microglia / citologia Doenças do Sistema Nervoso / genética Cartilagens Nasais |
topic |
Transtorno Autístico / genética Ácido Valproico / análise Microglia / citologia Doenças do Sistema Nervoso / genética Cartilagens Nasais |
description |
Most animal model studies of autism spectrum disorder (ASD) have been performed in males, which may be a reflex of the 3-times higher prevalence in boys than in girls. For this reason, little is known about the mechanisms underlying disease progression in females, and nothing is known about potential associations between microglial changes in the lateral septum (LS) and adult female cognition. Prenatal exposure to valproic acid (VPA) in mice has been widely used as an experimental model of autism-like behaviors associated with cellular changes. However, no study has reported the influence of VPA exposure in utero and its consequences on limbic system-dependent tasks or the microglial response in the LS in adult female mice. We compared the exploratory activity and risk assessment in novel environments of BALB/c control mice to mice exposed in utero to VPA and estimated the total number of microglia in the LS using an optical fractionator. On day 12.5 of pregnancy, females received diluted VPA or saline by gavage. After weaning, VPA exposed or control pups were separately housed in standard laboratory cages. At 5 months of age, all mice underwent behavioral testing and their brain sections were immunolabelled using IBA-1 antibody. In the open field test, VPA group showed a greater distance traveled, which was accompanied by less immobility, less time spent on the periphery and a greater number, crossed lines. Similar findings were found in the elevated plus maze test, where VPA mice traveled greater distances, immobility was significantly higher than that of control and VPA group spent less time on the closed arms of apparatus. Stereological analysis demonstrated higher microglial total number and density in the LS of VPA mice, as the cell count was greater, but the volume was similar. Therefore, we suggest that an increase in microglia in the LS may be part of the cellular changes associated with behavioral dysfunction in the VPA model of ASD. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-02-03T20:23:56Z |
dc.date.available.fl_str_mv |
2021-02-03T20:23:56Z |
dc.date.issued.fl_str_mv |
2021 |
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.citation.fl_str_mv |
LEÃO, Ellen Rose Leandro Ponce de et al. Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period. Journal of Chemical Neuroanatomy, v. 111, n. xx, p. xx, Jan. 2021. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4242 |
dc.identifier.issn.-.fl_str_mv |
0891-0618 |
dc.identifier.doi.-.fl_str_mv |
10.1016/j.jchemneu.2020.101875 |
identifier_str_mv |
LEÃO, Ellen Rose Leandro Ponce de et al. Lateral septum microglial changes and behavioral abnormalities of mice exposed to valproic acid during the prenatal period. Journal of Chemical Neuroanatomy, v. 111, n. xx, p. xx, Jan. 2021. 0891-0618 10.1016/j.jchemneu.2020.101875 |
url |
https://patua.iec.gov.br/handle/iec/4242 |
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eng |
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eng |
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Elsevier |
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Elsevier |
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