1. The epigenetic changes are affected by sex and valproic acid treatment in a rat model of post-traumatic stress disorder.
- Author
-
Akpınar G, Ketenci S, Sarıdoğan GE, Aydın B, Tekin N, Cabadak H, and Zafer Gören M
- Subjects
- Animals, Male, Female, Rats, Disease Models, Animal, Histones metabolism, Sex Characteristics, Hippocampus metabolism, Hippocampus drug effects, Acetylation drug effects, Anxiety drug therapy, Valproic Acid pharmacology, Stress Disorders, Post-Traumatic drug therapy, Stress Disorders, Post-Traumatic genetics, Stress Disorders, Post-Traumatic metabolism, Epigenesis, Genetic drug effects, Rats, Sprague-Dawley, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylase Inhibitors therapeutic use
- Abstract
Post-traumatic stress disorder (PTSD) presents distinct sex-specific differences in both symptom expression and treatment outcomes, with the underlying biological mechanisms still remain unclear. Epigenetic modifications, particularly histone acetylation, have been increasingly recognized as critical factors in the pathophysiology of PTSD. Valproic acid (VPA), a potent histone deacetylase (HDAC) inhibitor, has shown promise in modulating epigenetic responses and improving therapeutic outcomes is PTSD, though its effect may differ between sexes. This study aimed to explore the sex-specific epigenetic changes in response to trauma and the impact of VPA treatment in a rat model of PTSD induced by predator scent stress. Sprague-Dawley rats of both sexes were randomly assigned to stressed and non-stressed groups and treated with either VPA (100 mg/kg) or vehicle. Anxiety levels were assessed using the elevated plus maze, followed by analysis of histone H3 and H4 acetylation, HDAC activity, and c-fos expression in the hippocampus. Our findings revealed that traumatic stress led to increased freezing time and anxiety levels, with more pronounced effects observed in females. Additionally, we have identified sex-specific differences in hippocampal epigenetic modifications; stressed females exhibited higher H3 acetylation, and VPA-treated stressed males showed increased H4 acetylation. These results highlight the importance of considering sex differences in the epigenetic mechanism underlying PTSD and suggest that personalized therapeutic approaches may be necessary to address these complexities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF