Phasuk Sarayut, Varinthra Peeraporn, Nitjapol Andaman, Bandasak Korakod, Liu Ingrid Y
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan.
Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Antioxidants (Basel). 2021 Sep 4;10(9):1416. doi: 10.3390/antiox10091416.
Stress can elicit glucocorticoid release to promote coping mechanisms and influence learning and memory performance. Individual memory performance varies in response to stress, and the underlying mechanism is not clear yet. Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme participating in both physiological and pathological conditions. Several studies have demonstrated the correlation between PRDX6 expression level and stress-related disorders. Our recent finding indicates that lack of the gene leads to enhanced fear memory. However, it is unknown whether PRDX6 is involved in changes in anxiety response and memory performance upon stress. The present study reveals that hippocampal PRDX6 level is downregulated 30 min after acute immobilization stress (AIS) and trace fear conditioning (TFC). In human retinal pigment epithelium (ARPE-19) cells, the PRDX6 expression level decreases after being treated with stress hormone corticosterone. Lack of PRDX6 caused elevated basal HO levels in the hippocampus, basolateral amygdala, and medial prefrontal cortex, brain regions involved in anxiety response and fear memory formation. Additionally, this HO level was still high in the medial prefrontal cortex of the knockout mice under AIS. Anxiety behavior of mice was enhanced after immobilization for 30 min. After exposure to AIS before a contextual test, mice displayed a contextual fear memory deficit. Our results showed that the memory performance of mice was impaired when responding to AIS, accompanied by dysregulated HO levels. The present study helps better understand the function of PRDX6 in memory performance after acute stress.
应激可引发糖皮质激素释放，以促进应对机制并影响学习和记忆表现。个体的记忆表现会因应激而有所不同，其潜在机制尚不清楚。过氧化物酶体增殖物激活受体6（PRDX6）是一种参与生理和病理状况的多功能酶。多项研究已证实PRDX6表达水平与应激相关障碍之间的关联。我们最近的研究发现表明，该基因的缺失会导致恐惧记忆增强。然而，PRDX6是否参与应激时焦虑反应和记忆表现的变化尚不清楚。本研究表明，急性固定应激（AIS）和痕迹恐惧条件反射（TFC）后30分钟，海马体PRDX6水平下调。在人视网膜色素上皮（ARPE-19）细胞中，用应激激素皮质酮处理后PRDX6表达水平降低。PRDX6的缺失导致海马体、基底外侧杏仁核和内侧前额叶皮质（参与焦虑反应和恐惧记忆形成的脑区）的基础血红素加氧酶（HO）水平升高。此外，在AIS条件下，基因敲除小鼠内侧前额叶皮质的这种HO水平仍然很高。小鼠固定30分钟后焦虑行为增强。在情境测试前暴露于AIS后，小鼠表现出情境恐惧记忆缺陷。我们的结果表明，小鼠在应对AIS时记忆表现受损，同时伴有HO水平失调。本研究有助于更好地理解PRDX6在急性应激后记忆表现中的功能。
