Khalifeh Solmaz, Oryan Shahrbanoo, Digaleh Hadi, Shaerzadeh Fatemeh, Khodagholi Fariba, Maghsoudi Nader, Zarrindast Mohammad-Reza
Department of Animal Physiology, Faculty of Biology, Kharazmi (Tarbiat Moallem) University, Tehran, Iran,
J Mol Neurosci. 2015 Feb;55(2):492-9. doi: 10.1007/s12031-014-0370-z. Epub 2014 Jul 11.
Anxiety-related disorders are complex illnesses that underlying molecular mechanisms of these complicated emotional disorders are poorly understood. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important regulator of the antioxidant defense system. Its protective actions are not only limited to antioxidative transactivation, but also plays important roles in encountering various physiological and pathological stresses. In this study, we evaluated whether silencing of Nrf2 plays a role in development of anxiety-related behavior. In this regard, we exerted small interfering RNA (siRNA) targeting Nrf2 in dorsal third ventricle and subsequently examined the effect of this silencing on anxiety-related behavior along with supposed molecular mechanisms. Therefore, we evaluated apoptotic markers and mitochondrial electron transport chain (ETC) activity in three brain regions: hippocampus, amygdala, and prefrontal cortex. Based on our result, Nrf2-silenced rats exhibited greater anxiety-like behavior compared to control group. Furthermore, Nrf2 silencing increased activity of ETC complexes. Also, Bax/Bcl2 ratio of all mentioned areas of the brain and cleavage of caspase-3 in hippocampus increased in Nrf2 silenced group, however, with a distinct pattern.
焦虑相关障碍是复杂的疾病，这些复杂情绪障碍的潜在分子机制尚不清楚。核因子红细胞2相关因子2（Nrf2）是抗氧化防御系统最重要的调节因子。其保护作用不仅限于抗氧化反式激活，在应对各种生理和病理应激时也发挥重要作用。在本研究中，我们评估了Nrf2基因沉默是否在焦虑相关行为的发生中起作用。在这方面，我们将靶向Nrf2的小干扰RNA（siRNA）注入第三脑室背侧，随后研究这种沉默对焦虑相关行为的影响以及可能的分子机制。因此，我们评估了海马体、杏仁核和前额叶皮质这三个脑区的凋亡标志物和线粒体电子传递链（ETC）活性。根据我们的结果，与对照组相比，Nrf2基因沉默的大鼠表现出更强的焦虑样行为。此外，Nrf2基因沉默增加了ETC复合物的活性。而且，Nrf2基因沉默组中，上述所有脑区的Bax/Bcl2比值以及海马体中caspase-3的裂解均增加，但呈现出不同的模式。
