Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation

Detalhes bibliográficos
Autor(a) principal: Remor, Aline Pertile
Data de Publicação: 2019
Outros Autores: da Silva, Rodrigo Augusto [UNESP], de Matos, Filipe José, Glaser, Viviane, de Paula Martins, Roberta, Ghisoni, Karina, da Luz Scheffer, Débora, Andia, Denise Carleto, Portinho, Daniele [UNESP], de Souza, Ana Paula [UNESP], de Oliveira, Paulo Alexandre, Prediger, Rui Daniel, Torres, Alicia I., Linhares, Rose Marie Mueller, Walz, Roger, Ronsoni, Marcelo Fernando, Hohl, Alexandre, Rafacho, Alex, Aguiar, Aderbal Silva, De Paul, Ana Lucia, Latini, Alexandra
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s12035-018-1175-9
http://hdl.handle.net/11449/221096
Resumo: Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.
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spelling Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST InactivationCognitive deficitDNA methylationHyperglycemiaInflammation and oxidative stressMitochondrial dysfunctionChronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa e Inovação do Estado de Santa CatarinaConsejo Nacional de Investigaciones Científicas y TécnicasFondo para la Investigación Científica y TecnológicaLaboratório de Bioenergética e Estresse Oxidativo (LABOX) Departamento de Bioquímica Centro de Ciências Biológicas Universidade Federal de Santa Catarina (UFSC), Campus Universitário – Córrego Grande, Bloco C 201/214Programa de Pós-Graduação em Biociências e Saúde Área de Ciências da Vida Universidade do Oeste de Santa CatarinaLaboratório de Biologia Molecular Departamento de Morfologia Faculdade de Odontologia de Piracicaba Universidade Estadual de São PauloFaculdade de Odontologia Área de Pesquisa em Epigenética Universidade Paulista UNIPLaboratório Experimental de Doenças Neurodegenerativas Departamento de Farmacologia Centro de Ciências Biológicas UFSCCentro de Microscopía Electrónica Facultad de Ciencias Médicas Universidad Nacional de CórdobaConsejo Nacional de Investigaciones Cietificas y Técnicas (CONICET) Instituto de Investigaciones en Ciencias de la Salud (INICSA)Hospital Universitário Serviço de Endocrinologia Pediátrica Departamento de Pediatria UFSCHospital Infantil Joana de GusmãoCentro de Neurociências Aplicadas (CeNap) Departamento de Clínica Médica Hospital Universitário UFSCHospital Universitário Serviço de Endocrinologia e Metabologia Departamento de Clínica Médica UFSCLaboratório de Investigação de Doenças Crônicas Departamento de Fisiologia Centro de Ciências Biológicas UFSCHarvard Medical School Boston Children’s Hospital Center for Life Sciences Harvard UniversityLaboratório de Biologia Molecular Departamento de Morfologia Faculdade de Odontologia de Piracicaba Universidade Estadual de São PauloCAPES: 004_2013CAPES: 189405 16/2014CNPq: 479222/2013-4CAPES: 88881.062164/2014-01Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina: NENASC ProjectConsejo Nacional de Investigaciones Científicas y Técnicas: S/NFondo para la Investigación Científica y Tecnológica: S/NUniversidade Federal de Santa Catarina (UFSC)Universidade do Oeste de Santa CatarinaUniversidade Estadual Paulista (UNESP)UNIPUniversidad Nacional de CórdobaInstituto de Investigaciones en Ciencias de la Salud (INICSA)Hospital Infantil Joana de GusmãoHarvard UniversityRemor, Aline Pertileda Silva, Rodrigo Augusto [UNESP]de Matos, Filipe JoséGlaser, Vivianede Paula Martins, RobertaGhisoni, Karinada Luz Scheffer, DéboraAndia, Denise CarletoPortinho, Daniele [UNESP]de Souza, Ana Paula [UNESP]de Oliveira, Paulo AlexandrePrediger, Rui DanielTorres, Alicia I.Linhares, Rose Marie MuellerWalz, RogerRonsoni, Marcelo FernandoHohl, AlexandreRafacho, AlexAguiar, Aderbal SilvaDe Paul, Ana LuciaLatini, Alexandra2022-04-28T19:09:00Z2022-04-28T19:09:00Z2019-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1539-1557http://dx.doi.org/10.1007/s12035-018-1175-9Molecular Neurobiology, v. 56, n. 3, p. 1539-1557, 2019.1559-11820893-7648http://hdl.handle.net/11449/22109610.1007/s12035-018-1175-92-s2.0-85048580140Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecular Neurobiologyinfo:eu-repo/semantics/openAccess2022-04-28T19:09:00Zoai:repositorio.unesp.br:11449/221096Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:17:23.007049Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
title Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
spellingShingle Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
Remor, Aline Pertile
Cognitive deficit
DNA methylation
Hyperglycemia
Inflammation and oxidative stress
Mitochondrial dysfunction
title_short Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
title_full Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
title_fullStr Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
title_full_unstemmed Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
title_sort Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
author Remor, Aline Pertile
author_facet Remor, Aline Pertile
da Silva, Rodrigo Augusto [UNESP]
de Matos, Filipe José
Glaser, Viviane
de Paula Martins, Roberta
Ghisoni, Karina
da Luz Scheffer, Débora
Andia, Denise Carleto
Portinho, Daniele [UNESP]
de Souza, Ana Paula [UNESP]
de Oliveira, Paulo Alexandre
Prediger, Rui Daniel
Torres, Alicia I.
Linhares, Rose Marie Mueller
Walz, Roger
Ronsoni, Marcelo Fernando
Hohl, Alexandre
Rafacho, Alex
Aguiar, Aderbal Silva
De Paul, Ana Lucia
Latini, Alexandra
author_role author
author2 da Silva, Rodrigo Augusto [UNESP]
de Matos, Filipe José
Glaser, Viviane
de Paula Martins, Roberta
Ghisoni, Karina
da Luz Scheffer, Débora
Andia, Denise Carleto
Portinho, Daniele [UNESP]
de Souza, Ana Paula [UNESP]
de Oliveira, Paulo Alexandre
Prediger, Rui Daniel
Torres, Alicia I.
Linhares, Rose Marie Mueller
Walz, Roger
Ronsoni, Marcelo Fernando
Hohl, Alexandre
Rafacho, Alex
Aguiar, Aderbal Silva
De Paul, Ana Lucia
Latini, Alexandra
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de Santa Catarina (UFSC)
Universidade do Oeste de Santa Catarina
Universidade Estadual Paulista (UNESP)
UNIP
Universidad Nacional de Córdoba
Instituto de Investigaciones en Ciencias de la Salud (INICSA)
Hospital Infantil Joana de Gusmão
Harvard University
dc.contributor.author.fl_str_mv Remor, Aline Pertile
da Silva, Rodrigo Augusto [UNESP]
de Matos, Filipe José
Glaser, Viviane
de Paula Martins, Roberta
Ghisoni, Karina
da Luz Scheffer, Débora
Andia, Denise Carleto
Portinho, Daniele [UNESP]
de Souza, Ana Paula [UNESP]
de Oliveira, Paulo Alexandre
Prediger, Rui Daniel
Torres, Alicia I.
Linhares, Rose Marie Mueller
Walz, Roger
Ronsoni, Marcelo Fernando
Hohl, Alexandre
Rafacho, Alex
Aguiar, Aderbal Silva
De Paul, Ana Lucia
Latini, Alexandra
dc.subject.por.fl_str_mv Cognitive deficit
DNA methylation
Hyperglycemia
Inflammation and oxidative stress
Mitochondrial dysfunction
topic Cognitive deficit
DNA methylation
Hyperglycemia
Inflammation and oxidative stress
Mitochondrial dysfunction
description Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-01
2022-04-28T19:09:00Z
2022-04-28T19:09:00Z
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://dx.doi.org/10.1007/s12035-018-1175-9
Molecular Neurobiology, v. 56, n. 3, p. 1539-1557, 2019.
1559-1182
0893-7648
http://hdl.handle.net/11449/221096
10.1007/s12035-018-1175-9
2-s2.0-85048580140
url http://dx.doi.org/10.1007/s12035-018-1175-9
http://hdl.handle.net/11449/221096
identifier_str_mv Molecular Neurobiology, v. 56, n. 3, p. 1539-1557, 2019.
1559-1182
0893-7648
10.1007/s12035-018-1175-9
2-s2.0-85048580140
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Molecular Neurobiology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1539-1557
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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