Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/1822/45031 |
Resumo: | Objective: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. Methods: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. Results: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gammaaminobutyric acid levels, as compared with unseparated controls. Conclusion: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission. |
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Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in miceMaternal separationMalnutritionHippocampusLeptinIGF-1InflammationStereologyCiências Médicas::Medicina BásicaScience & TechnologyObjective: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. Methods: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. Results: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gammaaminobutyric acid levels, as compared with unseparated controls. Conclusion: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.This work was supported in part by National Institutes of Health (NIH) research grant 5R01HD053131, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH Office of Dietary Supplements, and Brazilian grants from CNPq and CAPES (Grant # RO1 HD053131). The authors would like to thank Dr. Patricia Foley for veterinarian technical support and Dr. Jose Paulo Andrade for the excellent comments and suggestions to improve this manuscript. N.S. contributed with the stereological studies. I.L.F. and R.B.O. contributed with the behavioral studies. I.L.F., R.B.O., and R.L.G. contributed with the study design, study analysis, and manuscript preparation. G.A.M. and P.B.F. contributed with neurochemical brain analyses. J.I.A.L. and G.M.A. contributed with hormonal and CRP serum analyses. D.G.C., K.M.C., and R.S.R. contributed with animal experimentation and data collection.Elsevier[et. al.]Universidade do MinhoFigueiredo, Ítalo LeiteFrota, Priscila B.Cunha, Davi G. daRaposo, Ramon da SilvaCanuto, Kildere M.Andrade, Geanne M. deSousa, NunoMoore, Sean R.Anstead, Gregory M.Alvarez-Leite, Jacqueline I.2016-092016-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/45031engFigueiredo, Í. L., Frota, P. B., da Cunha, D. G., da Silva Raposo, R., Canuto, K. M., de Andrade, G. M., . . . Oriá, R. B. (2016). Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice. Nutrition, 32(9), 1019-1027. doi: 10.1016/j.nut.2016.02.0160899-900710.1016/j.nut.2016.02.01627157468http://www.sciencedirect.com/science/article/pii/S0899900716001180info: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:RCAAP2023-07-21T12:46:04Zoai:repositorium.sdum.uminho.pt:1822/45031Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:44:00.414317Repositório 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 |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
title |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
spellingShingle |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice Figueiredo, Ítalo Leite Maternal separation Malnutrition Hippocampus Leptin IGF-1 Inflammation Stereology Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
title_full |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
title_fullStr |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
title_full_unstemmed |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
title_sort |
Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice |
author |
Figueiredo, Ítalo Leite |
author_facet |
Figueiredo, Ítalo Leite Frota, Priscila B. Cunha, Davi G. da Raposo, Ramon da Silva Canuto, Kildere M. Andrade, Geanne M. de Sousa, Nuno Moore, Sean R. Anstead, Gregory M. Alvarez-Leite, Jacqueline I. |
author_role |
author |
author2 |
Frota, Priscila B. Cunha, Davi G. da Raposo, Ramon da Silva Canuto, Kildere M. Andrade, Geanne M. de Sousa, Nuno Moore, Sean R. Anstead, Gregory M. Alvarez-Leite, Jacqueline I. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
[et. al.] Universidade do Minho |
dc.contributor.author.fl_str_mv |
Figueiredo, Ítalo Leite Frota, Priscila B. Cunha, Davi G. da Raposo, Ramon da Silva Canuto, Kildere M. Andrade, Geanne M. de Sousa, Nuno Moore, Sean R. Anstead, Gregory M. Alvarez-Leite, Jacqueline I. |
dc.subject.por.fl_str_mv |
Maternal separation Malnutrition Hippocampus Leptin IGF-1 Inflammation Stereology Ciências Médicas::Medicina Básica Science & Technology |
topic |
Maternal separation Malnutrition Hippocampus Leptin IGF-1 Inflammation Stereology Ciências Médicas::Medicina Básica Science & Technology |
description |
Objective: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. Methods: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. Results: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gammaaminobutyric acid levels, as compared with unseparated controls. Conclusion: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-09 2016-09-01T00:00:00Z |
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/1822/45031 |
url |
http://hdl.handle.net/1822/45031 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Figueiredo, Í. L., Frota, P. B., da Cunha, D. G., da Silva Raposo, R., Canuto, K. M., de Andrade, G. M., . . . Oriá, R. B. (2016). Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice. Nutrition, 32(9), 1019-1027. doi: 10.1016/j.nut.2016.02.016 0899-9007 10.1016/j.nut.2016.02.016 27157468 http://www.sciencedirect.com/science/article/pii/S0899900716001180 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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