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Nano-selenium and the SRC family kinases pathway: Redefining gene expression dynamics in major depressive disorder based on a randomized controlled trial

Articles in Press

Document Type : Original Article

Authors

1 Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

2 Psychosomatic Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran Department of Psychiatry, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Hematology and Blood Banking, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

5 Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

6 Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran Nutritional Sciences Research Center, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background: Major depressive disorder (MDD) is a prevalent psychiatric condition. Dysregulation of signaling pathways interacting with SRC family kinases has been implicated in the pathophysiology of MDD through inflammation. Nano-selenium, a nanoscale form of selenium with enhanced bioavailability, has the potential to modulate oxidative stress and inflammation, which are implicated in MDD. To the best of our knowledge, in this study, for the first time we aimed to examine whether nano-selenium supplementation would decrease c-SRC gene expression.
Methods: This triple-blind, randomized, placebo-controlled clinical trial was conducted at Imam Khomeini Hospital Complex, Tehran, Iran. Using block randomization, fifty participants diagnosed with MDD per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria were randomly assigned to receive nano-selenium (55 µg/day, n = 25) or placebo (n = 25) for 12 weeks alongside sertraline (50 mg/day). c-SRC gene expression was assessed using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) from peripheral blood samples collected at baseline and after 12 weeks.
Results: Twenty-one participants in each group completed the study, with an 84% retention rate in both groups. No serious adverse events were reported. There was no significant difference between groups at baseline. Post-intervention, c-SRC gene expression levels decreased in both the nano-selenium and placebo groups [median change (Q1, Q3): -0.0031, (-0.0065, -0.0005) vs. -0.0021 (-0.0085, 0), respectively; P < 0.05]; however, no significant differences were observed between the two groups (P = 0.606).
Conclusion: Nano-selenium supplementation did not significantly modulate c-SRC gene expression. Limitations included a short duration. Future studies should explore alternative molecular pathways, higher supplementation doses, and treatment-naïve populations to better understand nano-selenium’s therapeutic potential in MDD.

Keywords

Main Subjects

References
  1. Li Z, Ruan M, Chen J, Fang Y. Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications. Neurosci Bull 2021; 37(6): 863-80.
  2. Organization WH. Depressive disorder (depression) [Online]. [cited 2025 Jan 15]; Available from: URL: https://www.who.int/news-room/fact-sheets/detail/depression.
  3. Voineskos D, Daskalakis ZJ, Blumberger DM. Management of Treatment-Resistant Depression: Challenges and Strategies. Neuropsychiatr Dis Treat 2020; 16: 221-34.
  4. Machado-Vieira R, Salvadore G, Luckenbaugh DA, Manji HK, Zarate CA, Jr. Rapid onset of antidepressant action: A new paradigm in the research and treatment of major depressive disorder. J Clin Psychiatry 2008; 69(6): 946-58.
  5. Rice E. Understanding the Lived Experiences of People with Sexual Difficulties Resulting from Using and Discontinuing Antidepressants. Ottawa, ON: University of Ottawa; 2023.
  6. Jiang Y, Zou D, Li Y, Gu S, Jie D, Ma X, et al. Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders. Pharm 2022; 15(10): 1203.
  7. Liu JJ, Wei YB, Strawbridge R, Bao Y, Chang S, Shi L, et al. Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis. Mol Psychiatry 2020; 25(2): 339-50.
  8. Gałecka M, Szemraj J, Su KP, Halaris A, Maes M, Skiba A, et al. Is the JAK-STAT Signaling Pathway Involved in the Pathogenesis of Depression? J Clin Med 2022; 11(7).
  9. Negi P, Cheke RS, Patil VM. Recent advances in pharmacological diversification of Src family kinase inhibitors. Egypt J Med Hum Genet 2021; 22(1): 52.
  10. Hu X, Li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther 2021; 6(1): 402.
  11. Nie L, Ma D, Quinn JP, Wang M. Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation. J Headache Pain 2021; 22(1): 146.
  12. Zhu W-Q, Li B-J, Cui R-J. Antidepressant-like effect of 5-O-methylvisammioside targeting SRC is accompanied by hippocampal neuroinflammation reduction in lipopolysaccharide-challenged mice [Online]. [cited 2023 Dec 31]; Available from: URL: https://ouci.dntb.gov.ua/en/works/7AKGPDkl.
  13. Nie L, Ye WR, Chen S, Chirchiglia D, Wang M. Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain. Curr Neuropharmacol 2021; 19(5): 665-78.
  14. Chen W, Zhang G, Marvizón JC. NMDA receptors in primary afferents require phosphorylation by Src family kinases to induce substance P release in the rat spinal cord. Neuroscience 2010; 166(3): 924-34.
  15. Salter MW, Pitcher GM. Dysregulated Src upregulation of NMDA receptor activity: a common link in chronic pain and schizophrenia. Febs j 2012; 279(1): 2-11.
  16. Paul R, Angele B, Popp B, Klein M, Riedel E, Pfister HW, et al. Differential regulation of blood-brain barrier permeability in brain trauma and pneumococcal meningitis-role of Src kinases. Exp Neurol 2007; 203(1): 158-67.
  17. Mychasiuk R, Muhammad A, Kolb B. Chronic stress induces persistent changes in global DNA methylation and gene expression in the medial prefrontal cortex, orbitofrontal cortex, and hippocampus. Neuroscience 2016; 322: 489-99.
  18. Marchetti MC, Di Marco B, Cifone G, Migliorati G, Riccardi C. Dexamethasone-induced apoptosis of thymocytes: role of glucocorticoid receptor-associated Src kinase and caspase-8 activation. Blood 2003; 101(2): 585-93.
  19. Gage MC, Thippeswamy T. Inhibitors of Src Family Kinases, Inducible Nitric Oxide Synthase, and NADPH Oxidase as Potential CNS Drug Targets for Neurological Diseases. CNS Drugs 2021; 35(1): 1-20.
  20. Tridente G, Jana A, Nath A, Ashraf GM. Protein kinase inhibitors as therapeutics in neurodegenerative and psychiatric disorders: progress, challenges, and recommendations. 1st In: Mansour HM, Khattab MM, El-khatib AS, editors. Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders. Amsterdam, The Netherlands: Elsevier; 2023. p. 403-573.
  21. Haura EB. SRC and STAT pathways. J Thorac Oncol 2006; 1(5): 403-5.
  22. Zambonino MC, Quizhpe EM, Mouheb L, Rahman A, Agathos SN, Dahoumane SA. Biogenic Selenium Nanoparticles in Biomedical Sciences: Properties, Current Trends, Novel Opportunities and Emerging Challenges in Theranostic Nanomedicine. Nanomaterials (Basel) 2023; 13(3): 424.
  23. Casaril AM, Domingues M, Bampi SR, Lourenço DA, Smaniotto T, Segatto N, et al. The antioxidant and immunomodulatory compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole attenuates depression-like behavior and cognitive impairment developed in a mouse model of breast tumor. Brain Behav Immun 2020; 84: 229-41.
  24. Casaril AM, Domingues M, Bampi SR, de Andrade Lourenço D, Padilha NB, Lenardão EJ, et al. The selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole reverses depressive-like behavior induced by acute restraint stress in mice: modulation of oxido-nitrosative stress and inflammatory pathway. Psychopharmacology (Berl) 2019; 236(10): 2867-80.
  25. Ashraf H, Cossu D, Ruberto S, Noli M, Jasemi S, Simula ER, et al. Latent Potential of Multifunctional Selenium Nanoparticles in Neurological Diseases and Altered Gut Microbiota. Materials (Basel) 2023; 16(2): 699.
  26. Ali HFH, El-Sayed NM, Khodeer DM, Ahmed AAM, Hanna PA, Moustafa YMA. Nano selenium ameliorates oxidative stress and inflammatory response associated with cypermethrin-induced neurotoxicity in rats. Ecotoxicol Environ Saf 2020; 195: 110479.
  27. Yang J, Li H, Hao Z, Jing X, Zhao Y, Cheng X, et al. Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway. ACS Appl Mater Interfaces 2022; 14(3): 3685-700.
  28. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23(1): 56-62.
  29. Michael B, Williams JBW, Karg RS, Spitzer RL. Structured clinical interview for DSM-5 disorders: SCID-5-CV clinician version. Washington, DC: American Psychiatric Association Publishing; 2016.
  30. Farrokhian A, Bahmani F, Taghizadeh M, Mirhashemi SM, Aarabi MH, Raygan F, et al. Selenium Supplementation Affects Insulin Resistance and Serum hs-CRP in Patients with Type 2 Diabetes and Coronary Heart Disease. Horm Metab Res 2016; 48(4): 263-8.
  31. Milanowski L, Rasul F, Gajda SN, Eyileten C, Siller-Matula J, Postula M. Genetic Variability of SRC Family Kinases and Its Association with Platelet Hyperreactivity and Clinical Outcomes: A Systematic Review. Curr Pharm Des 2018; 24(5): 628-40.
  32. Qian X, Li Y, Liu X, Tu R, Tian Z, Zhang H, et al. C-src tyrosine kinase gene rs1378942 polymorphism and hypertension in Asians: Review and meta-analysis. Clin Chim Acta 2018; 487: 202-9.
  33. Lu Y, Xu X, Jiang T, Jin L, Zhao XD, Cheng JH, et al. Sertraline ameliorates inflammation in CUMS mice and inhibits TNF-α-induced inflammation in microglia cells. Int Immunopharmacol 2019; 67: 119-28.
  34. Saadaldin Alkasso RA, Abdullah Al Neaimy KS. The Effect of Sertraline on Oxidative Stress in Patients with Depression. Mosul J Nurs 2021; 9(2): 248-56.
  35. Önal HT, Yetkin D, Ayaz F. Exploring the immunomodulatory effects of sertraline: Cytokine modulation and signaling pathway dynamics. J Neuroimmunol 2025; 399: 578514.
  36. Wang L, Wang R, Liu L, Qiao D, Baldwin DS, Hou R. Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: A systematic review and meta-analysis. Brain Behav Immun 2019; 79: 24-38.
  37. Al-Hakeim HK, Twayej AJ, Al-Dujaili AH, Maes M. Plasma Indoleamine-2,3-Dioxygenase (IDO) is Increased in Drug-Naï ve Major Depressed Patients and Treatment with Sertraline and Ketoprofen Normalizes IDO in Association with Pro-Inflammatory and Immune- Regulatory Cytokines. CNS Neurol Disord Drug Targets 2020; 19(1): 44-54.
  38. Rosas-Sánchez GU, Germán-Ponciano LJ, Guillen-Ruiz G, Cueto-Escobedo J, Limón-Vázquez AK, Rodríguez-Landa JF, et al. Neuroplasticity and Mechanisms of Action of Acute and Chronic Treatment with Antidepressants in Preclinical Studies. Biomedicines 2024; 12(12): 2744.
  39. Mariani N, Cattane N, Pariante C, Cattaneo A. Gene expression studies in Depression development and treatment: An overview of the underlying molecular mechanisms and biological processes to identify biomarkers. Transl Psychiatry 2021; 11(1): 354.
  40. Einoch R, Weinreb O, Mandiuk N, Youdim MBH, Bilker W, Silver H. The involvement of BDNF-CREB signaling pathways in the pharmacological mechanism of combined SSRI- antipsychotic treatment in schizophrenia. Eur Neuropsychopharmacol 2017; 27(5): 470-83.
  41. Athira KV, Bandopadhyay S, Samudrala PK, Naidu VGM, Lahkar M, Chakravarty S. An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective. Curr Neuropharmacol 2020; 18(3): 168-87.
  42. Levander OA. Scientific rationale for the 1989 recommended dietary allowance for selenium. J Am Diet Assoc 1991; 91(12): 1572-6.
  43. Kostis JB, Dobrzynski JM. Limitations of Randomized Clinical Trials. Am J Cardiol 2020; 129: 109-15.
  44. Seehusen DA, Reeves MM, Fomin DA. Cerebrospinal fluid analysis. Am Fam Physician 2003; 68(6): 1103-8.
  45. Hatami-Fard G, Anastasova-Ivanova S. Advancements in Cerebrospinal Fluid Biosensors: Bridging the Gap from Early Diagnosis to the Detection of Rare Diseases. Sensors (Basel) 2024; 24(11): 3294.
  46. Holland NT, Smith MT, Eskenazi B, Bastaki M. Biological sample collection and processing for molecular epidemiological studies. Mutat Res 2003; 543(3): 217-34.
  47. Deisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S, et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 2006; 13(9): 913-22.
  48. Leonardson AS, Zhu J, Chen Y, Wang K, Lamb JR, Reitman M, et al. The effect of food intake on gene expression in human peripheral blood. Hum Mol Genet 2010; 19(1): 159-69.
  49. Hosnedlova B, Kepinska M, Skalickova S, Fernandez C, Ruttkay-Nedecky B, Peng Q, et al. Nano-selenium and its nanomedicine applications: a critical review. Int J Nanomedicine 2018; 13: 2107-28.
  50. Rezaeimanesh N, Rafiee P, Saeedi R, Khosravian P, Sahraian MA, Eskandarieh S, et al. The effect of crocin-selenium nanoparticles on the cognition and oxidative stress markers of multiple sclerosis patients: a randomized triple-blinded placebo-controlled clinical trial. Biometals 2024; 37(2): 305-19.
Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 04 March 2025
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