Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus
Autor(a) principal: | |
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Data de Publicação: | 2013 |
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/10316/109780 https://doi.org/10.1371/journal.pone.0065515 |
Resumo: | Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose) for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal neurons, which may lead to changes in synaptic proteins, thus contributing to changes in hippocampal neurotransmission and to cognitive and memory impairments. |
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Diabetes alters KIF1A and KIF5B motor proteins in the hippocampusAnalysis of VarianceAnimalsAxonal TransportBlotting, WesternBrain Diseases, MetabolicCells, CulturedDNA PrimersDiabetes Mellitus, ExperimentalDyneinsFluorescent Antibody TechniqueHippocampusImmunohistochemistryKinesinsMaleRatsRats, WistarReal-Time Polymerase Chain ReactionDiabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose) for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal neurons, which may lead to changes in synaptic proteins, thus contributing to changes in hippocampal neurotransmission and to cognitive and memory impairments.Public Library of Science2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109780http://hdl.handle.net/10316/109780https://doi.org/10.1371/journal.pone.0065515eng1932-6203Baptista, Filipa I.Pinto, Maria J.Elvas, FilipeAlmeida, Ramiro D.Ambrósio, A. Franciscoinfo: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:RCAAP2023-10-26T09:49:21Zoai:estudogeral.uc.pt:10316/109780Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:55.683316Repositório 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 |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
title |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
spellingShingle |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus Baptista, Filipa I. Analysis of Variance Animals Axonal Transport Blotting, Western Brain Diseases, Metabolic Cells, Cultured DNA Primers Diabetes Mellitus, Experimental Dyneins Fluorescent Antibody Technique Hippocampus Immunohistochemistry Kinesins Male Rats Rats, Wistar Real-Time Polymerase Chain Reaction |
title_short |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
title_full |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
title_fullStr |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
title_full_unstemmed |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
title_sort |
Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus |
author |
Baptista, Filipa I. |
author_facet |
Baptista, Filipa I. Pinto, Maria J. Elvas, Filipe Almeida, Ramiro D. Ambrósio, A. Francisco |
author_role |
author |
author2 |
Pinto, Maria J. Elvas, Filipe Almeida, Ramiro D. Ambrósio, A. Francisco |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Baptista, Filipa I. Pinto, Maria J. Elvas, Filipe Almeida, Ramiro D. Ambrósio, A. Francisco |
dc.subject.por.fl_str_mv |
Analysis of Variance Animals Axonal Transport Blotting, Western Brain Diseases, Metabolic Cells, Cultured DNA Primers Diabetes Mellitus, Experimental Dyneins Fluorescent Antibody Technique Hippocampus Immunohistochemistry Kinesins Male Rats Rats, Wistar Real-Time Polymerase Chain Reaction |
topic |
Analysis of Variance Animals Axonal Transport Blotting, Western Brain Diseases, Metabolic Cells, Cultured DNA Primers Diabetes Mellitus, Experimental Dyneins Fluorescent Antibody Technique Hippocampus Immunohistochemistry Kinesins Male Rats Rats, Wistar Real-Time Polymerase Chain Reaction |
description |
Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose) for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal neurons, which may lead to changes in synaptic proteins, thus contributing to changes in hippocampal neurotransmission and to cognitive and memory impairments. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 |
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/10316/109780 http://hdl.handle.net/10316/109780 https://doi.org/10.1371/journal.pone.0065515 |
url |
http://hdl.handle.net/10316/109780 https://doi.org/10.1371/journal.pone.0065515 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
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) |
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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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