Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy.
Department of Physical Therapy and Rehabilitation Science; Brain and Spinal Injury Center, University of California at San Francisco, San Francisco, CA, USA.
Psychopharmacology (Berl). 2022 Aug;239(8):2547-2557. doi: 10.1007/s00213-022-06140-6. Epub 2022 Apr 23.
Although the occurrence of stressful events is very common during life, their impact may be different depending on the experience severity and duration. Specifically, acute challenges may trigger adaptive responses and even improve the individual's performance. However, such a physiological positive coping can only take place if the underlying molecular mechanisms are properly functioning. Indeed, if these systems are compromised by genetic factors or previous adverse conditions, the response set in motion by an acute challenge may be maladaptive and even cause the insurgence or the relapse of stress-related psychiatric disorders.
On these bases, we evaluated in the rat brain the role of the antioxidant component of the redox machinery on the acute stress responsiveness and its modulation by potential detrimental or beneficial events.
The expression of several antioxidant enzymes was assessed in different brain areas of adult male rats exposed to acute stress 3 weeks after a chronic immobilization paradigm with or without a concomitant treatment with the antipsychotic lurasidone.
The acute challenge was able to trigger a marked antioxidant response that, despite the washout period, was impaired by the previous adverse experience and restored by lurasidone in an anatomical-specific manner.
We found that a working antioxidant machinery takes part in acute stress response and may be differentially affected by other experiences. Given the essential role of stress responsiveness in almost every life process, the identification of the underlying mechanisms and their potential pharmacological modulation add further translational value to our data.
尽管生活中应激事件的发生非常普遍，但它们的影响可能因经历的严重程度和持续时间而异。具体来说，急性挑战可能会引发适应性反应，甚至提高个体的表现。然而，如果潜在的分子机制正常运作，这种生理上的积极应对才有可能发生。事实上，如果这些系统因遗传因素或先前的不利条件而受损，急性挑战引发的反应可能是适应不良的，甚至会导致与压力相关的精神障碍的发作或复发。
基于这些发现，我们在大鼠大脑中评估了氧化还原机制的抗氧化成分在急性应激反应中的作用，以及潜在的有害或有益事件对其的调节作用。
在慢性束缚范式后 3 周暴露于急性应激的成年雄性大鼠的不同大脑区域中评估了几种抗氧化酶的表达，同时评估了是否同时进行了抗精神病药鲁拉西酮治疗。
急性挑战能够引发明显的抗氧化反应，尽管有冲洗期，但先前的不利经历会损害这种反应，而鲁拉西酮则以解剖特异性的方式恢复了这种反应。
我们发现，一个运作良好的抗氧化机制参与了急性应激反应，并且可能会受到其他经历的不同影响。鉴于应激反应在几乎每一个生命过程中的重要作用，对潜在机制的识别及其潜在的药理学调节为我们的数据增加了更多的转化价值。
