Department of Medical Biology, Meram Faculty of Medicine, University of Konya-NE, Konya, Turkey.
Department of Medical Pharmacology, Meram Faculty of Medicine, University of Konya-NE, 42080, Akyokus, Meram, Konya, Turkey.
Mol Neurobiol. 2022 Nov;59(11):7036-7044. doi: 10.1007/s12035-022-03026-8. Epub 2022 Sep 8.
Depression is one of the most important and serious health problems in developing countries which affects millions of people. It is associated with the decrease of the quality of life as well as suicides and mortality. The disease may show recurrent episodes in some patients. Obviously, not all the patients with depression could be treated properly, because some individuals are drug-resistant and the options for the therapy are limited. Therefore, it is crucial to investigate new molecules and pathways that may have possible antidepressant activity. Sirtuin (SIRT), known as a class III histone deacetylase, which is regulated by nicotinamide adenine dinucleotide (NAD +), is one of these molecules. In the current study, we investigated the possible antidepressant-like effect of SIRT2 inhibitor AK-7. For this purpose, behavioral tests were performed in chronic AK-7-treated mice, and the expression levels of BDNF, NGF, NTF3, CREB, NTRK2, ERK1, ERK2, and GAP43 genes were evaluated by qRT-PCR analysis in brain tissues. Protein levels for BDNF, CREB1, and NTRK2 were determined by western blot. Our data showed that AK-7 significantly decreased immobility time and showed antidepressant-like effect. In addition, AK-7 treatment significantly increased mRNA levels of CREB and NTRK2 and protein levels of CREB1, BDNF, and NTRK2. Finally, our results suggest that SIRT2 and AK-7 may have a potential role in the cellular mechanisms of depression.
抑郁症是发展中国家最重要和最严重的健康问题之一，影响着数百万人。它与生活质量下降以及自杀和死亡率有关。这种疾病可能会在一些患者中反复发作。显然，并非所有的抑郁症患者都能得到适当的治疗，因为有些个体对药物有抗药性，治疗选择有限。因此，研究新的分子和途径可能具有潜在的抗抑郁活性至关重要。Sirtuin（SIRT），又称 III 类组蛋白去乙酰化酶，受烟酰胺腺嘌呤二核苷酸（NAD+）调节，是其中一种分子。在目前的研究中，我们研究了 SIRT2 抑制剂 AK-7 可能具有的抗抑郁样作用。为此，我们在慢性 AK-7 治疗的小鼠中进行了行为测试，并通过 qRT-PCR 分析评估了大脑组织中 BDNF、NGF、NTF3、CREB、NTRK2、ERK1、ERK2 和 GAP43 基因的表达水平。通过 Western blot 测定 BDNF、CREB1 和 NTRK2 的蛋白水平。我们的数据表明，AK-7 显著减少了不动时间并表现出抗抑郁样作用。此外，AK-7 治疗显著增加了 CREB 和 NTRK2 的 mRNA 水平以及 CREB1、BDNF 和 NTRK2 的蛋白水平。最后，我们的结果表明，SIRT2 和 AK-7 可能在抑郁症的细胞机制中发挥作用。
