Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner

Exercise stimulates the release of metabolites from the liver and muscles known as "exercise factors" into the circulation. The benefits of exercise on cognition are mediated by an increase in brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Identifying these exercise-re...

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Main Author: El Masri, Diala (author)
Format: masterThesis
Published: 2023
Subjects:
Online Access:http://hdl.handle.net/10725/15278
https://doi.org/10.26756/th.2023.635
http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php
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author El Masri, Diala
author_facet El Masri, Diala
author_role author
dc.creator.none.fl_str_mv El Masri, Diala
dc.date.none.fl_str_mv 2023
2023-07-31
2024-01-22T11:27:29Z
2024-01-22T11:27:29Z
dc.identifier.none.fl_str_mv http://hdl.handle.net/10725/15278
https://doi.org/10.26756/th.2023.635
http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php
dc.language.none.fl_str_mv en
dc.publisher.none.fl_str_mv Lebanese American University
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Memory consolidation
Cognition--Effect of exercise on
Histones
Lebanese American University--Dissertations
Dissertations, Academic
dc.title.none.fl_str_mv Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
dc.type.none.fl_str_mv Thesis
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/masterThesis
description Exercise stimulates the release of metabolites from the liver and muscles known as "exercise factors" into the circulation. The benefits of exercise on cognition are mediated by an increase in brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Identifying these exercise-related factors could provide a detailed insight on the processes by which exercise exerts its positive effects on cognition. Previous work has shown that the levels of citrate, a Kreb’s cycle intermediate, are increased in the circulation upon exercise. In this study, we tested whether exogenous administration of citrate enhances learning and memory formation in a sex-dependent manner and elucidated the underlying molecular mechanisms. Our results show that citrate enhances associative memory formation in male mice, but not female mice. In males. citrate is released by the muscles during exercise, crosses the blood-brain barrier and induces TrkB overexpression in the hippocampus. In fact, we found that citrate-dependent enhancement of learning and memory is linked to an increase in hippocampal histone acetylation, specifically acetylation of histone H4. This increase is accompanied with a decrease in hippocampal HDAC2, leading to the expression of immediate early genes involved in synaptic plasticity. Overall, our findings suggest that citrate may be an endogenous molecule that mediates exercise-induced memory formation in male mice.
eu_rights_str_mv openAccess
format masterThesis
id LAURepo_3fceb9347844ffeab49abbdbc629d233
language_invalid_str_mv en
network_acronym_str LAURepo
network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/15278
publishDate 2023
publisher.none.fl_str_mv Lebanese American University
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
spelling Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent mannerEl Masri, DialaMemory consolidationCognition--Effect of exercise onHistonesLebanese American University--DissertationsDissertations, AcademicExercise stimulates the release of metabolites from the liver and muscles known as "exercise factors" into the circulation. The benefits of exercise on cognition are mediated by an increase in brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Identifying these exercise-related factors could provide a detailed insight on the processes by which exercise exerts its positive effects on cognition. Previous work has shown that the levels of citrate, a Kreb’s cycle intermediate, are increased in the circulation upon exercise. In this study, we tested whether exogenous administration of citrate enhances learning and memory formation in a sex-dependent manner and elucidated the underlying molecular mechanisms. Our results show that citrate enhances associative memory formation in male mice, but not female mice. In males. citrate is released by the muscles during exercise, crosses the blood-brain barrier and induces TrkB overexpression in the hippocampus. In fact, we found that citrate-dependent enhancement of learning and memory is linked to an increase in hippocampal histone acetylation, specifically acetylation of histone H4. This increase is accompanied with a decrease in hippocampal HDAC2, leading to the expression of immediate early genes involved in synaptic plasticity. Overall, our findings suggest that citrate may be an endogenous molecule that mediates exercise-induced memory formation in male mice.1 online resource (xi, 55 leaves): ill. (some col.)Includes bibliographical references (leaves 43-55)Lebanese American University2024-01-22T11:27:29Z2024-01-22T11:27:29Z20232023-07-31Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/15278https://doi.org/10.26756/th.2023.635http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.phpeninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/152782024-01-22T11:28:31Z
spellingShingle Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
El Masri, Diala
Memory consolidation
Cognition--Effect of exercise on
Histones
Lebanese American University--Dissertations
Dissertations, Academic
status_str publishedVersion
title Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
title_full Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
title_fullStr Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
title_full_unstemmed Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
title_short Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
title_sort Exercise-induced Citrate Enhances Associative Memory Formation by Modulating Histone Acetylation in a Sex-dependent manner
topic Memory consolidation
Cognition--Effect of exercise on
Histones
Lebanese American University--Dissertations
Dissertations, Academic
url http://hdl.handle.net/10725/15278
https://doi.org/10.26756/th.2023.635
http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php