Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , |
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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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 |
|
_version_ |
1808129047285202944 |