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给予母体催产素可减轻遭受围产期创伤的青少年后代的伤害感受、社交及表观遗传损伤。

Maternal oxytocin administration mitigates nociceptive, social, and epigenetic impairments in adolescent offspring exposed to perinatal trauma.

作者信息

Harris Sydney, Kodila Zoe, Salberg Sabrina, Sgro Marissa, Vlassopoulos Elaina, Li Crystal N, Smith Madeleine J, Shultz Sandy R, Yamakawa Glenn R, Noel Melanie, Mychasiuk Richelle

机构信息

Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.

Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia; Centre for Trauma and Mental Health Research, Vancouver Island University, Nanaimo, B.C., Canada.

出版信息

Neurotherapeutics. 2025 Apr 22:e00598. doi: 10.1016/j.neurot.2025.e00598.

Abstract

Adverse childhood experiences (ACEs) alter brain development, leading to vulnerability for chronic pain, mental health disorders, and suicidality. These effects often emerge during adolescence. Importantly, ACEs can occur prenatally, including when exposed to in utero intimate partner violence (IPV) or postnatally as maternal neglect. Maternal social support has demonstrated promise in the mitigation of ACE-related deficits. Oxytocin, which has a role in social-bonding and stress regulation, serves as a suitable surrogate for social support in preclinical studies. Therefore, we aimed to explore the effects of oxytocin on alleviating social deficits, nociception, and epigenetic changes resulting from models that aimed to mimic the stress normally induced following exposure to two ACEs: IPV in utero and maternal neglect. During pregnancy, dams were randomly assigned to experience the model of IPV or a sham insult. Following birth, offspring from the IPV group underwent 10 days of maternal separation. Dams received three days of oxytocin therapy while nursing. In adolescence, half of the offspring underwent a plantar surgery to induce pain. Overall, in adolescence, rats exposed to the ACEs exhibited increased nociceptive sensitivity and aberrant social interactions, particularly among males, further suggesting that ACEs can increase an individual's risk for chronic pain. The ACEs changed gene expression related to social behaviour and neuroplasticity. Maternal oxytocin normalized pain, social, and gene changes, while oxytocin levels in offspring correlated with nociceptive sensitivity. Although ACEs have enduring consequences, the outcomes are modifiable, and oxytocin may be a robust and implementable therapeutic capable of attenuating early adversity.

摘要

童年不良经历(ACEs)会改变大脑发育,导致易患慢性疼痛、心理健康障碍和自杀倾向。这些影响通常在青春期出现。重要的是,ACEs可在产前发生,包括暴露于子宫内亲密伴侣暴力(IPV)时,或产后发生,如母亲忽视。母亲的社会支持已显示出减轻与ACEs相关缺陷的前景。催产素在社会联系和应激调节中起作用,在临床前研究中可作为社会支持的合适替代物。因此,我们旨在探讨催产素对减轻社会缺陷、伤害感受和表观遗传变化的影响,这些变化源于旨在模拟暴露于两种ACEs(子宫内IPV和母亲忽视)后通常诱发的应激的模型。在怀孕期间,将母鼠随机分配以经历IPV模型或假损伤。出生后,IPV组的后代经历10天的母婴分离。母鼠在哺乳期间接受三天的催产素治疗。在青春期,一半的后代接受足底手术以诱导疼痛。总体而言,在青春期,暴露于ACEs的大鼠表现出伤害感受敏感性增加和异常的社会互动,尤其是在雄性大鼠中,这进一步表明ACEs会增加个体患慢性疼痛的风险。ACEs改变了与社会行为和神经可塑性相关的基因表达。母体催产素使疼痛、社会和基因变化恢复正常,而后代的催产素水平与伤害感受敏感性相关。尽管ACEs有持久的后果,但这些结果是可改变的,催产素可能是一种强大且可实施的治疗方法,能够减轻早期逆境的影响。

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