Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Departments of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran.
Neurochem Res. 2021 May;46(5):1252-1263. doi: 10.1007/s11064-021-03263-8. Epub 2021 Feb 12.
Depression is a disabling psychiatric disorder affecting millions of people all around the world. Under current therapeutic choices, a portion of patients are not responsive, have relapses, or experience cognitive side effects. Hence, the present study aimed to find other antidepressant compounds lacking the mentioned deficiency. Since epigenetic regulations have attracted more attention in etiology of depression, histone deacetylase (HDAC) inhibitors have gained more importance due to their possible antidepressant activity. We selected a promising member of HDAC inhibitors named suberanilohydroxamic acid (SAHA) to evaluate its antidepressant properties. Early life stress disarrays many neurodevelopmental factors and consequently, leads to the destruction of hippocampus and prefrontal cortex synapses as areas highly related to emotion and memory so that any destruction on them can cause lasting impairments. For that reason, we used maternal separation (MS) paradigm to investigate depression in male mice. To compare the efficacy of SAHA with current treatment options, we also treated a group of MS mice with fluoxetine (FLX) as first-line pharmacological drugs of depression. The results demonstrated that depressive-like behavior, cognitive function and inflammatory response of MS mice were attenuated with SAHA. Our data showed that, besides anti-depressant and cognition-boosting effects similar to FLX, SAHA counteracted inflammatory response caused by depression and reversed the coenzyme Q (CoQ) level in hippocampus. SAHA's effect on alleviating depressive behavior was accompanied with memory enhancement and hippocampus biochemical tests. These findings may propose SAHA as another therapeutic option for depressive symptoms, especially with comorbid cognitive impairment.
抑郁症是一种使人丧失能力的精神疾病，影响着全世界数百万人。在目前的治疗选择中，一部分患者没有反应，病情复发，或出现认知副作用。因此，本研究旨在寻找其他缺乏上述缺陷的抗抑郁化合物。由于表观遗传调控在抑郁症的病因学中引起了更多的关注，组蛋白去乙酰化酶（HDAC）抑制剂因其可能的抗抑郁活性而受到更多的重视。我们选择了一种有前途的 HDAC 抑制剂，即琥珀酸氨羟肟酸（SAHA），来评估其抗抑郁特性。早期生活压力扰乱了许多神经发育因素，从而导致海马体和前额叶皮质突触的破坏，因为这些区域与情绪和记忆密切相关，所以它们的任何破坏都会导致持久的损伤。因此，我们使用母婴分离（MS）范式来研究雄性小鼠的抑郁症。为了比较 SAHA 与当前治疗选择的疗效，我们还用氟西汀（FLX）治疗了一组 MS 小鼠，作为治疗抑郁症的一线药物。结果表明，SAHA 可减轻 MS 小鼠的抑郁样行为、认知功能和炎症反应。我们的数据表明，除了与 FLX 相似的抗抑郁和增强认知作用外，SAHA 还能对抗抑郁引起的炎症反应，并逆转海马体中的辅酶 Q（CoQ）水平。SAHA 缓解抑郁行为的作用伴随着记忆增强和海马体生化测试。这些发现可能为 SAHA 提供了另一种治疗抑郁症的选择，特别是伴有认知障碍的抑郁症。
