Maternal Separation-Induced Histone Acetylation Correlates with BDNF-Programmed Synaptic Changes in an Animal Model of P
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Maternal Separation-Induced Histone Acetylation Correlates with BDNF-Programmed Synaptic Changes in an Animal Model of PTSD with Sex Differences Haoran Sun 1 & Xianqiang Zhang 2,3 & Yujia Kong 4 & Luping Gou 2 & Bo Lian 5 & Yanyu Wang 2 & Li Jiang 6 & Qi Li 7 & Hongwei Sun 2 & Lin Sun 2 Received: 22 May 2020 / Accepted: 19 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Maternal separation (MS) causes long-lasting epigenetic changes in the brain and increases vulnerability to traumatic events in adulthood. Of interest, there may be sex-specific differences in these epigenetic changes. In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF were measured to determine whether BDNF influences risk of PTSD following MS in early life. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2~PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). In animals stressed with the SPS procedure in adulthood, those that had increased MS intensity in childhood demonstrated more significant changes in performance on tests of anxiety, depression, and contextual fear memory. Reduced levels of total BDNF mRNA and protein were observed after SPS treatment and further declined in groups with greater MS time in childhood. Interestingly, these changes were correlated with decreased H3K9ac levels and increased HDAC2 levels. Additional MS also led to more severe ultrastructural synaptic damage in rats that experienced the SPS procedure, particularly in the CA1 and CA3 region of the HIP, reflecting impaired synaptic plasticity in these regions. Interestingly, male rats in the MS3h-PTSD group showed decreased anxiety, but no similar changes were found in female rats, suggesting a degree of gender specificity in coping with stress after mild MS. In summary, this study suggests that the epigenetic signatures of the BDNF genes can be linked to HIP responses to stress, providing insights that may be relevant for people at risk of stress-related psychopathologies. Keywords Maternal separation (MS) . Post-traumatic stress disorder (PTSD) . Brain-derived neurotrophic factor (BDNF) . Histone acetylation . Histone deacetylase 2(HDAC2) . Synaptic ultrastructure
Introduction Post-traumatic stress disorder (PTSD) is a serious, debilitating mental disorder that can occur following a traumatic event or
* Lin Sun [email protected] 1
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School of Clinical Medicine, Weifang Medical University, 7166# Baotong West Street, Weifang 261053, Shandong, People’s Republic of China School of Psychology, Weifang Medical University, 7166# Baotong West Street, Weifang 261053, Shandong, People’s Republic of China National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital/Institute of Mental Health and the Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing 100083, People’s Republic of China
exposure to a traumatic environment [1]. As on
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