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SAHA Improves Depressive Symptoms, Cognitive Impairment and Oxidative Stress: Rise of a New Antidepressant Class

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Abstract

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 Q10 (CoQ10) 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.

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Acknowledgements

This work was supported by grants from the deputy of research of Zanjan University of Medical Sciences (Grant NO: A-12-769-18) and research grant from Tehran University of Medical Sciences, Tehran, Iran (Grant NO: 42068-158-01-98).

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  1. Amir Sasan Bayani Ershadi

    Present address: Departments of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran

  2. Hossein Amini-Khoei

    Present address: Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, P. O. Box: 88138-33435, Shahrekord, Iran

  3. Ahmad Reza Dehpour

    Present address: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran

Authors and Affiliations

  1. Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

    Amir Sasan Bayani Ershadi & Mir-Jamal Hosseini

  2. Departments of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran

    Mir-Jamal Hosseini

  3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Reza Dehpour

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  1. Amir Sasan Bayani Ershadi
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Ershadi, A.S.B., Amini-Khoei, H., Hosseini, MJ. et al. SAHA Improves Depressive Symptoms, Cognitive Impairment and Oxidative Stress: Rise of a New Antidepressant Class. Neurochem Res 46, 1252–1263 (2021). https://doi.org/10.1007/s11064-021-03263-8

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