Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy

The therapeutic potential of aerobic exercise in mitigating seizures and cognitive issues in temporal lobe epilepsy (TLE) is recognized, yet the underlying mechanisms are not well understood. Using a rodent TLE model induced by Kainic acid (KA), we investigated the impact of a single bout of exercis...

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Main Authors: Silvienne C. Sint Jago, Rudhab Bahabry, Anna Maria Schreiber, Julia Homola, Tram Ngyuen, Fernando Meijia, Jane B. Allendorfer, Farah D. Lubin
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Epilepsy & Behavior Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589986423000606
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author Silvienne C. Sint Jago
Rudhab Bahabry
Anna Maria Schreiber
Julia Homola
Tram Ngyuen
Fernando Meijia
Jane B. Allendorfer
Farah D. Lubin
author_facet Silvienne C. Sint Jago
Rudhab Bahabry
Anna Maria Schreiber
Julia Homola
Tram Ngyuen
Fernando Meijia
Jane B. Allendorfer
Farah D. Lubin
author_sort Silvienne C. Sint Jago
collection DOAJ
description The therapeutic potential of aerobic exercise in mitigating seizures and cognitive issues in temporal lobe epilepsy (TLE) is recognized, yet the underlying mechanisms are not well understood. Using a rodent TLE model induced by Kainic acid (KA), we investigated the impact of a single bout of exercise (i.e., acute) or 4 weeks of aerobic exercise (i.e., chronic). Blood was processed for epilepsy-associated serum markers, and DNA methylation (DNAme), and hippocampal area CA3 was assessed for gene expression levels for DNAme-associated enzymes. While acute aerobic exercise did not alter serum Brain-Derived Neurotrophic Factor (BDNF) or Interleukin-6 (IL-6), chronic exercise resulted in an exercise-specific decrease in serum BDNF and an increase in serum IL-6 levels in epileptic rats. Additionally, whole blood DNAme levels, specifically 5-hydroxymethylcytosine (5-hmC), decreased in epileptic animals following chronic exercise. Hippocampal CA3 5-hmC levels and ten-eleven translocation protein (TET1) expression mirrored these changes. Furthermore, immunohistochemistry analysis revealed that most 5-hmC changes in response to chronic exercise were neuron-specific within area CA3 of the hippocampus. Together, these findings suggest that DNAme mechanisms in the rodent model of TLE are responsive to chronic aerobic exercise, with emphasis on neuronal 5-hmC DNAme in the epileptic hippocampus.
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spelling doaj.art-870e488345bc4496980870f0197d40e42024-03-03T04:30:05ZengElsevierEpilepsy & Behavior Reports2589-98642024-01-0125100642Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsySilvienne C. Sint Jago0Rudhab Bahabry1Anna Maria Schreiber2Julia Homola3Tram Ngyuen4Fernando Meijia5Jane B. Allendorfer6Farah D. Lubin7Department of Neurobiology, University of Alabama at Birmingham, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United States; Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Neurobiology, University of Alabama at Birmingham, United States; Corresponding author at: Department of Neurobiology, Shelby Building, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, United States.The therapeutic potential of aerobic exercise in mitigating seizures and cognitive issues in temporal lobe epilepsy (TLE) is recognized, yet the underlying mechanisms are not well understood. Using a rodent TLE model induced by Kainic acid (KA), we investigated the impact of a single bout of exercise (i.e., acute) or 4 weeks of aerobic exercise (i.e., chronic). Blood was processed for epilepsy-associated serum markers, and DNA methylation (DNAme), and hippocampal area CA3 was assessed for gene expression levels for DNAme-associated enzymes. While acute aerobic exercise did not alter serum Brain-Derived Neurotrophic Factor (BDNF) or Interleukin-6 (IL-6), chronic exercise resulted in an exercise-specific decrease in serum BDNF and an increase in serum IL-6 levels in epileptic rats. Additionally, whole blood DNAme levels, specifically 5-hydroxymethylcytosine (5-hmC), decreased in epileptic animals following chronic exercise. Hippocampal CA3 5-hmC levels and ten-eleven translocation protein (TET1) expression mirrored these changes. Furthermore, immunohistochemistry analysis revealed that most 5-hmC changes in response to chronic exercise were neuron-specific within area CA3 of the hippocampus. Together, these findings suggest that DNAme mechanisms in the rodent model of TLE are responsive to chronic aerobic exercise, with emphasis on neuronal 5-hmC DNAme in the epileptic hippocampus.http://www.sciencedirect.com/science/article/pii/S2589986423000606EpigeneticsNeuronsAstrocytes5-hydroxymethylcytosineTen-eleven translocationChronic exercise
spellingShingle Silvienne C. Sint Jago
Rudhab Bahabry
Anna Maria Schreiber
Julia Homola
Tram Ngyuen
Fernando Meijia
Jane B. Allendorfer
Farah D. Lubin
Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
Epilepsy & Behavior Reports
Epigenetics
Neurons
Astrocytes
5-hydroxymethylcytosine
Ten-eleven translocation
Chronic exercise
title Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
title_full Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
title_fullStr Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
title_full_unstemmed Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
title_short Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
title_sort aerobic exercise alters dna hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy
topic Epigenetics
Neurons
Astrocytes
5-hydroxymethylcytosine
Ten-eleven translocation
Chronic exercise
url http://www.sciencedirect.com/science/article/pii/S2589986423000606
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