Tang Chunling, Hu Jian
Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.
Nanoscale Res Lett. 2021 Feb 10;16(1):28. doi: 10.1186/s11671-021-03477-3.
Researches pivoting on histone deacetylases (HDACs) in depression have been excessively conducted, but not much on HDAC1. Therein, the present study is launched to disclose the mechanism of HDAC1/microRNA (miR)-124-5p/neuropeptide Y (NPY) axis in depression. Sprague Dawley rats were stimulated by chronic unpredictable mild stress to establish depression models. Depressed rats were injected with inhibited HDAC1 or suppressed miR-124-5p to explore their roles in body weight, learning and memory abilities, oxidative stress and inflammation in serum and neurotransmitter expression in hippocampal tissues. MiR-124-5p, HDAC1 and NPY expression in the hippocampus were tested. The interactions of miR-124-5p, HDAC1 and NPY expression were also confirmed. Higher miR-124-5p and HDAC1 and lower NPY expression levels were found in the hippocampus of depressed rats. Inhibited miR-124-5p or suppressed HDAC1 attenuated learning and memory abilities and increased body weight of depressed rats. Knockdown of miR-124-5p or inhibition of HDAC1 suppressed oxidative stress and inflammation and promoted neurotransmitter expression of depressed rats. HDAC1 mediated miR-124-5p to regulate NPY. Knockdown of NPY abolished the protective effects of inhibited miR-124-5p on depressed rats. Our study illustrates that suppression of either miR-124-5p or HDAC1 up-regulates NPY to improve memory and learning abilities in depressed mice, which may update the existed knowledge of depression and provide a novel reference for treatment of depression.
关于抑郁症中组蛋白去乙酰化酶（HDACs）的研究已经开展得很多了，但针对HDAC1的研究却不多。在此，本研究旨在揭示HDAC1/微小RNA（miR）-124-5p/神经肽Y（NPY）轴在抑郁症中的作用机制。采用慢性不可预测温和应激刺激Sprague Dawley大鼠建立抑郁症模型。给抑郁大鼠注射HDAC1抑制剂或miR-124-5p抑制剂，以探究它们在体重、学习和记忆能力、血清氧化应激和炎症以及海马组织神经递质表达方面的作用。检测海马中miR-124-5p、HDAC1和NPY的表达。还证实了miR-124-5p、HDAC1和NPY表达之间的相互作用。抑郁大鼠海马中miR-124-5p和HDAC1表达较高，NPY表达较低。抑制miR-124-5p或抑制HDAC1可减轻抑郁大鼠的学习和记忆能力，并增加其体重。敲低miR-124-5p或抑制HDAC1可抑制抑郁大鼠的氧化应激和炎症，并促进神经递质表达。HDAC1介导miR-124-5p来调节NPY。敲低NPY可消除抑制miR-124-5p对抑郁大鼠的保护作用。我们的研究表明，抑制miR-124-5p或HDAC1均可上调NPY，从而改善抑郁小鼠的记忆和学习能力，这可能更新现有的抑郁症知识，并为抑郁症治疗提供新的参考。
