Over the past decade, critical, non-redundant roles of the ten-eleven translocation (TET) family of dioxygenase enzymes have been identified in the brain during developmental and postnatal stages. Specifically, TET-mediated active demethylation, involving the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine and subsequent oxidative derivatives, is dynamically regulated in response to environmental stimuli such as neuronal activity, learning and memory processes, and stressor exposure. Such changes may therefore perpetuate stable and dynamic transcriptional patterns within neuronal populations required for neuroplasticity and behavioural adaptation. In this review, we will highlight recent evidence supporting a role of TET protein function and active demethylation in stress-induced neuroepigenetic and behavioural adaptations. We further explore potential mechanisms by which TET proteins may mediate both the basal and pathological embedding of stressful life experiences within the brain of relevance to stress-related psychiatric disorders.

在过去的十年中，在发育和出生后阶段在大脑中发现了双加氧酶的 10-11 易位 (TET) 家族的关键、非冗余作用。具体而言，TET 介导的主动去甲基化，涉及 5-甲基胞嘧啶反复氧化为 5-羟甲基胞嘧啶和随后的氧化衍生物，响应于环境刺激（如神经元活动、学习和记忆过程以及压力源暴露）而动态调节。因此，这种变化可能会使神经可塑性和行为适应所需的神经元群内的稳定和动态转录模式永久化。在这篇综述中，我们将强调支持 TET 蛋白功能和主动去甲基化在压力诱导的神经表观遗传和行为适应中的作用的最新证据。