Al Abed Alice Shaam, Allen Tiarne Vickie, Ahmed Noorya Yasmin, Sellami Azza, Sontani Yovina, Rawlinson Elise Caitlin, Marighetto Aline, Desmedt Aline, Dehorter Nathalie
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
The Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
iScience. 2024 Apr 16;27(5):109747. doi: 10.1016/j.isci.2024.109747. eCollection 2024 May 17.
A rising concern in autism spectrum disorder (ASD) is the heightened sensitivity to trauma, the potential consequences of which have been overlooked, particularly upon the severity of the ASD traits. We first demonstrate a reciprocal relationship between ASD and post-traumatic stress disorder (PTSD) and reveal that exposure to a mildly stressful event induces PTSD-like memory in four mouse models of ASD. We also establish an unanticipated consequence of stress, as the formation of PTSD-like memory leads to the aggravation of core autistic traits. Such a susceptibility to developing PTSD-like memory in ASD stems from hyperactivation of the prefrontal cortex and altered fine-tuning of parvalbumin interneuron firing. Traumatic memory can be treated by recontextualization, reducing the deleterious effects on the core symptoms of ASD in the KO mouse model. This study provides a neurobiological and psychological framework for future examination of the impact of PTSD-like memory in autism.
自闭症谱系障碍（ASD）中一个日益受到关注的问题是对创伤的高度敏感性，其潜在后果一直被忽视，尤其是对ASD特征严重程度的影响。我们首先证明了ASD与创伤后应激障碍（PTSD）之间的相互关系，并揭示了在四种ASD小鼠模型中，暴露于轻度应激事件会诱发类似PTSD的记忆。我们还发现了应激的一个意外后果，即类似PTSD的记忆形成会导致核心自闭症特征的加重。ASD中易形成类似PTSD记忆的这种易感性源于前额叶皮质的过度激活和小白蛋白中间神经元放电微调的改变。创伤性记忆可以通过重新情境化来治疗，从而减少对KO小鼠模型中ASD核心症状的有害影响。这项研究为未来研究类似PTSD的记忆对自闭症的影响提供了一个神经生物学和心理学框架。
